Note the word chronic.
This is also being used as a drug to help MS patients walk, see here:
http://ir.acorda.com/phoenix.zhtml?c=194451&p=irol-newsOtherArticle&ID=1701026&highlight=
This does bring up the question, if it helps stroke patients does that mean that demyelination occurs as part of the stroke damage?
http://ir.acorda.com/phoenix.zhtml?c=194451&p=irol-newsOtherArticle&ID=1656337&highlight=
Acorda Therapeutics, Inc. (Nasdaq: ACOR)
presented data showing that treatment with dalfampridine improved motor
function in a preclinical model of stroke, with treatment initiated at
least four weeks following the ischemic event. These data were presented
on February 2 at the American Heart Association/American Stroke
Association International Stroke Conference in New Orleans, LA.
Dalfampridine, also known as 4-aminopyridine, is the active chemical
ingredient in AMPYRA® (dalfampridine) Extended Release
Tablets, 10 mg.
“These are the first preclinical data to show an oral pharmacologic
treatment can improve function in chronic, or long term, stroke. We are
excited by these results and plan to begin proof-of-concept human
clinical trials of AMPYRA in people with chronic stroke later this
year,” said Andrew R. Blight, Ph.D., Acorda Therapeutics’ Chief
Scientific Officer. “The majority of the nearly seven million people in
the United States who live with the long term effects of a stroke have
motor function deficits, such as walking impairment, but there are no
established treatments other than physical therapy to address these
impairments.”
A late-breaking science presentation, entitled “Dalfampridine Improves
Sensorimotor Function in Rats with Chronic Deficits Following Middle
Cerebral Artery Occlusion,” presented by Acorda scientist Jennifer Iaci,
reviewed data from three study groups that received treatment beginning
four weeks after a permanent middle cerebral artery occlusion (pMCAO).
The neurological impairments that result are expected to be permanent by
four weeks, which represents the chronic stage of stroke. Each group
received three treatment phases over the course of the study: high and
low doses of dalfampridine, and placebo. The order of the treatment
phases was different for each group, with a 10 day washout period
between each phase.
Researchers assessed functional improvement using a battery of standard
motor function tests in both the forelimbs and hind limbs. In each of
the three study groups, treatment with dalfampridine resulted in
significant improvement in function compared to placebo across all
measures during the respective treatment periods. Improvements in the
high dose phase were consistently better than those seen in the low dose
phase.
“In addition to the seven million Americans living with the consequences
of a prior stroke, there are close to 800,000 people in the United
States who have new stroke events each year. The resulting disability
has a major impact on the person who suffers the stroke as well as on
their caregivers, and places a significant burden on the healthcare
system,” said Seth Finklestein, M.D., Chairman and Chief Scientific
Officer of Biotrofix, a preclinical research organization that conducted
research for this study in partnership with Acorda. “These are the first
data from a well-controlled preclinical study that have demonstrated
improvement in motor function related to walking and upper body
movement. Developing a therapeutic option that can improve function
would represent a potential major advance in the standard of care for
stroke survivors.”
Acorda plans to begin a proof-of-concept trial of AMPYRA in stroke by
the end of 2012. (I'm going to try to find out how to get involved)Go here to apply for the trial:
http://oc1dean.blogspot.com/2012/06/phase-1phase-2-study-of-dalfampridine.html
This study will evaluate the use of AMPYRA in stroke
patients with chronic neurologic deficits, including walking impairment.
AMPYRA is approved in the United States as a treatment to improve
walking in patients with multiple sclerosis (MS). This was demonstrated
by an improvement in walking speed. AMPYRA is known as prolonged-,
modified-, or sustained-release fampridine (FAMPYRA®) in some
countries outside the United States.
Important Safety Information
AMPYRA can cause seizures; the risk of seizures increases with
increasing AMPYRA doses. AMPYRA is contraindicated in patients with a
prior history of seizure. Discontinue AMPYRA use if seizure occurs.
AMPYRA is contraindicated in patients with moderate or severe renal
impairment (CrCl less-than or equal to 50 mL/min); the risk of seizures
in patients with mild renal impairment (CrCl 51-80 mL/min) is unknown,
but AMPYRA plasma levels in these patients may approach those seen at a
dose of 15 mg twice daily, a dose that may be associated with an
increased risk of seizures; estimated CrCl should be known before
initiating treatment with AMPYRA.
AMPYRA should not be taken with other forms of 4-aminopyridine (4-AP,
fampridine), since the active ingredient is the same.
Urinary tract infections were reported more frequently as adverse
reactions in patients receiving AMPYRA 10 mg twice daily compared to
placebo.
The most common adverse events (incidence greater-than or equal to 2%
and at a rate greater than the placebo rate) for AMPYRA in MS patients
were urinary tract infection, insomnia, dizziness, headache, nausea,
asthenia, back pain, balance disorder, multiple sclerosis relapse,
paresthesia, nasopharyngitis, constipation, dyspepsia, and
pharyngolaryngeal pain.
For full U.S. Prescribing Information and Medication Guide for AMPYRA,
please visit: www.AMPYRA.com.
About Acorda
Therapeutics
Acorda Therapeutics is a biotechnology company focused on developing
therapies that restore function and improve the lives of people with MS,
spinal cord injury and other neurological conditions.
Acorda markets AMPYRA®
(dalfampridine) Extended Release Tablets, 10 mg, in the United
States as a treatment to improve walking in patients with multiple
sclerosis (MS). This was demonstrated by an improvement in walking
speed. AMPYRA is marketed outside the United States as FAMPYRA® (prolonged-release
fampridine tablets) by Biogen Idec under a licensing
agreement from Acorda. AMPYRA and FAMPYRA are sold under a license from
Alkermes Pharma Ireland Limited and manufactured by Alkermes Pharma
Ireland Limited and other parties.
The Company also markets ZANAFLEX
CAPSULES® (tizanidine hydrochloride) and Zanaflex
tablets, a short-acting drug for the management of spasticity.
Acorda is developing an industry-leading pipeline of novel neurological
therapies. The Company is studying AMPYRA to improve a range of
functional impairments caused by MS, as well as its use in other
neurological conditions, including cerebral palsy and chronic stroke. In
addition, Acorda is developing clinical stage compounds AC105 for acute
treatment of spinal cord injury and GGF2(see here for GGF2) for treatment of heart
failure. GGF2 is also being investigated in preclinical studies as a
treatment for neurological conditions such as stroke and spinal cord
injury. Additional preclinical programs include rHIgM22, a remyelinating
monoclonal antibody for the treatment of MS, and chondroitinase, an
enzyme that encourages nerve plasticity in spinal cord injury.
Ask your doctor, this was reported on Feb. 3, 2012 so they should be well aware of this by now.
Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 29,356 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Thursday, May 31, 2012
5 New Heart Tests That Could Save Your Life
We should probably consider asking our doctors about these. Full descriptions at the caring.com link.
http://www.caring.com/articles/new-heart-tests-that-could-save-your-life
http://www.caring.com/articles/new-heart-tests-that-could-save-your-life
1. Coronary artery calcium scan (CAC)
Calcium is one of the main components in the plaque that builds up inside coronary arteries, narrowing and stiffening them and obstructing blood flow to and through the heart. A CAC score of zero is considered ideal; a score over 400 indicates severe atherosclerosis. Although CAC scanning is still one of the lesser-known heart tests, a study in the New England Journal of Medicine a few years ago determined that the CAC test was a "strong predictor" of heart attack and fatal heart disease. The researchers followed close to 7,000 people, testing them for CAC, then followed them for more than three years, correlating the data with the number of fatal or life-threatening coronary events. Those whose scores ranged from 100 to 300 were seven times more likely to die of a heart attack or other heart ailment than those with low CAC scores, and those with scores over 300 were even more at risk.2. Corus CAD
A genetic test, as opposed to a physical measurement, Corus CAD looks for evidence of narrowing or blockage in the coronary arteries at the molecular level. Blood samples are screened for the activity of 23 genes that exhibit changes when there's an obstruction in the arteries. It's gender specific, taking into account differences in how men and women respond to obstructive coronary artery disease.3. High-sensitivity C-reactive protein assay
Levels of C-reactive protein in the blood rise when there's widespread inflammation somewhere in the body. This can be due to bacterial or viral infection, but inflammation can also occur when plaque buildup irritates and inflames artery walls. Research shows that elevated levels of CRP correlate with increased risk of heart attack and fatal heart disease, possibly because inflammation damages and fragments arterial plaque, causing tiny portions of plaque to break off and be released into the bloodstream, leading to heart attack or stroke.4. Carotid artery IMT ultrasound (C-IMT)
One of the newest heart health tests to reach doctor's offices is a specialized, high-resolution ultrasound of the carotid artery called C-IMT. C-IMT uses sophisticated computer software to calculate the thickness of the intima and media, two layers of the lining of the carotid artery. Studies have found a strong correlation between the health of carotid arteries in the neck and the coronary arteries in the heart.5. Hemoglobin A1c test
The newest and least-known of the heart tests listed here is actually an extremely common test for diabetes, but it's only recently been used to detect heart disease. Also called glycated hemoglobin or glycosylated hemoglobin, the hemoglobin A1c test (HbA1c) is considered a measure of average blood sugar levels over time. More specifically, it measures the percentage of hemoglobin -- a protein in red blood cells that carries oxygen -- that's coated with sugar (glycated). The higher the A1C level, the poorer your blood sugar control.
Labels:
blood work,
C-IMT,
CAC,
Corus CAD,
doctor question,
HbA1c,
heart,
prevention
Wednesday, May 30, 2012
Matt Monarch: Recovery from Stroke and Heart Attack with Raw Foods
Cause and effect of raw foods to recovery from stroke makes no sense. He just luckily had a minor stroke.
http://www.theguruofyou.com/videolibrary/25-raw_food_gurus/42-matt_monarch/606-matt_monarch_recovery_from_stroke_and_heart_attack_with_raw_foods/
http://www.theguruofyou.com/videolibrary/25-raw_food_gurus/42-matt_monarch/606-matt_monarch_recovery_from_stroke_and_heart_attack_with_raw_foods/
Erythropoietin Amplifies Stroke-Induced Oligodendrogenesis in the Rat
I like the last lines, they would have helped me tremendously. But this might require the knowledge of what white matter damage you have vs. gray matter damage.
Erythropoietin Amplifies Stroke-Induced Oligodendrogenesis in the Rat
Background
Erythropoietin (EPO), a hematopoietic cytokine, enhances neurogenesis and angiogenesis during stroke recovery. In the present study, we examined the effect of EPO on oligodendrogenesis in a rat model of embolic focal cerebral ischemia.Methodology and Principal Findings
Recombinant human EPO (rhEPO) at a dose of 5,000 U/kg (n = 18) or saline (n = 18) was intraperitoneally(In mammals, the serous membrane lining the cavity of the abdomen and that is folded over the viscera.) administered daily for 7 days starting 24 h after stroke onset. Treatment with rhEPO augmented actively proliferating oligodendrocyte progenitor cells (OPCs) measured by NG2 immunoreactive cells within the peri-infarct white matter and the subventricular zone (SVZ), but did not protect against loss of myelinating oligodendrocytes measured by cyclic nucleotide phosphodiesterase (CNPase) positive cells 7 days after stroke. However, 28 and 42 days after stroke, treatment with rhEPO significantly increased myelinating oligodendrocytes and myelinated axons within the peri-infarct white matter. Using lentivirus to label subventricular zone (SVZ) neural progenitor cells, we found that in addition to the OPCs generated in the peri-infarct white matter, SVZ neural progenitor cells contributed to rhEPO-increased OPCs in the peri-infarct area. Using bromodeoxyuridine (BrdU) for birth-dating cells, we demonstrated that myelinating oligodendrocytes observed 28 days after stroke were derived from OPCs. Furthermore, rhEPO significantly improved neurological outcome 6 weeks after stroke. In vitro, rhEPO increased differentiation of adult SVZ neural progenitor cells into oligodendrocytes and enhanced immature oligodendrocyte cell proliferation.Conclusions
Our in vivo and in vitro data indicate that EPO amplifies stroke-induced oligodendrogenesis that could facilitate axonal re-myelination and lead to functional recovery after stroke.Urinary Proteomics to Support Diagnosis of Stroke
Rather than arguing with ER doctors about your belief you've had a stroke, just hand them a container of your pee. For guys they probably couldn't even stand up long enough, with the additional problem of only one hand to hold the pee cup and your penis. They could rule out drug interactions also. Something similar would need to be done for bleeds. How long after onset of stroke were samples taken? How much faster and accurate than a MRI?
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035879
Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (−0.30 to 1.25) in cases compared to −1.04 (IQR −1.86 to −0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035879
Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (−0.30 to 1.25) in cases compared to −1.04 (IQR −1.86 to −0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials.
Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke
The precursor research to this post:
Someone should make a hypothesis of what sensory stimulation on humans would be equivalent(face, hands,genitals?) to a whisker on a rat. This would be so easy to implement and run research on.
Despite progress in reducing ischemic stroke damage, complete protection
remains elusive. Here we demonstrate that, after permanent occlusion of
a major cortical artery (middle cerebral artery; MCA), single whisker
stimulation can induce complete protection of the adult rat cortex, but
only if administered within a critical time window. Animals that receive
early treatment are histologically and behaviorally equivalent to
healthy controls and have normal neuronal function. Protection of the
cortex clearly requires reperfusion to the ischemic area despite
permanent occlusion. Using blood flow imaging and other techniques we
found evidence of reversed blood flow into MCA branches from an
alternate arterial source via collateral vessels (inter-arterial
connections), a potential mechanism for reperfusion. These findings
suggest that the cortex is capable of extensive blood flow
reorganization and more importantly that mild sensory stimulation can
provide complete protection from impending stroke given early
intervention. Such non-invasive, non-pharmacological intervention has
clear translational potential.
Question; Does the infarct location also include motor cortex? white matter? pre-motor cortex? Just trying to see how massive a stroke was generated. They should have cubic volumes listed someplace.
Recruiting adaptive cellular stress responses for successful brain ageing
This summary from the Dana foundation is much clearer than the abstract. I'm not sure how to use this information but we need more studies on it for stroke rehab.
Several studies have demonstrated that regular exercise helps protect the brain from age-related decline. But in a recent essay published in the March 2012 issue of Nature Reviews Neuroscience, Mark Mattson, a neuroscientist at the National Institute of Aging, argues that diet is just as important. Specifically, he cites results demonstrating that intermittent fasting—one day on food, the next day off of it—can also protect the brain. So why might abstaining from food every 24 hours be such a brain benefit?
“Fasting is a challenge to the nervous system, to the energy regulating systems,” says Mattson. “And what we’re thinking, from the standpoint of evolution, is that animals living in the wild, including our ancestors, often had to go extended time periods without food. If you haven’t had food for a while, your mind becomes more active—it has to become very active, to help you figure out how to find food.”
That activity manifests itself in neuroplasticity; in mouse models, Mattson and colleagues have shown that intermittent fasting helps protect the brain from both oxidative stress and direct injury. Those protective effects result in the upregulation of brain-derived neurotrophic factor (BDNF) as well as anti-oxidants, DNA-repair enzymes, and other gene products that help promote plasticity and survival of neurons over time.
“It makes evolutionary sense that caloric availability would have an impact, not just on brain regions involved in metabolism, such as the hypothalamus, but also on brain regions involved in learning, such as the hippocampus,” says Alexis Stranahan, a professor at Georgia Health Sciences University and Mattson’s co-author on the Nature Reviews Neuroscience essay. “Your mind needs to be sharp if you are looking for food. At the other end of the spectrum, it also makes sense that an overabundance of food would dull the senses, making it harder to form associations.”
In the past, some studies suggested that caloric restriction promoted good health—and researchers have seen improved outcomes in animal models of Alzheimer’s disease, Parkinson’s disease, stroke and Huntington’s disease by simply reducing the number of calories an animal eats each day by a significant percentage. But Mattson argues that, when it comes to the brain, fasting may be more effective. “We find that the intermittent fasting increases neurogenesis while limited daily reduction in calories has very little effect,” he says. “BDNF levels are increased in response to both exercise and intermittent energy restriction.”
Abstract here:
http://www.nature.com/nrn/journal/v13/n3/abs/nrn3151.html
No self-medication here.
Several studies have demonstrated that regular exercise helps protect the brain from age-related decline. But in a recent essay published in the March 2012 issue of Nature Reviews Neuroscience, Mark Mattson, a neuroscientist at the National Institute of Aging, argues that diet is just as important. Specifically, he cites results demonstrating that intermittent fasting—one day on food, the next day off of it—can also protect the brain. So why might abstaining from food every 24 hours be such a brain benefit?
“Fasting is a challenge to the nervous system, to the energy regulating systems,” says Mattson. “And what we’re thinking, from the standpoint of evolution, is that animals living in the wild, including our ancestors, often had to go extended time periods without food. If you haven’t had food for a while, your mind becomes more active—it has to become very active, to help you figure out how to find food.”
That activity manifests itself in neuroplasticity; in mouse models, Mattson and colleagues have shown that intermittent fasting helps protect the brain from both oxidative stress and direct injury. Those protective effects result in the upregulation of brain-derived neurotrophic factor (BDNF) as well as anti-oxidants, DNA-repair enzymes, and other gene products that help promote plasticity and survival of neurons over time.
“It makes evolutionary sense that caloric availability would have an impact, not just on brain regions involved in metabolism, such as the hypothalamus, but also on brain regions involved in learning, such as the hippocampus,” says Alexis Stranahan, a professor at Georgia Health Sciences University and Mattson’s co-author on the Nature Reviews Neuroscience essay. “Your mind needs to be sharp if you are looking for food. At the other end of the spectrum, it also makes sense that an overabundance of food would dull the senses, making it harder to form associations.”
In the past, some studies suggested that caloric restriction promoted good health—and researchers have seen improved outcomes in animal models of Alzheimer’s disease, Parkinson’s disease, stroke and Huntington’s disease by simply reducing the number of calories an animal eats each day by a significant percentage. But Mattson argues that, when it comes to the brain, fasting may be more effective. “We find that the intermittent fasting increases neurogenesis while limited daily reduction in calories has very little effect,” he says. “BDNF levels are increased in response to both exercise and intermittent energy restriction.”
Abstract here:
http://www.nature.com/nrn/journal/v13/n3/abs/nrn3151.html
No self-medication here.
New Mini-sensor Measures Magnetic Field of the Brain
Our researchers now will be able to listen in on our brain waves and maybe compare them to normal ones.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=120619&CultureCode=en
Successful test at PTB of optical magnetometer with potential applications in brain imaging for neurological diagnostics and in basic research.
In future a new magnetic sensor the size of a sugar cube might simplify the measurement of brain activity. In the magnetically shielded room of Physikalisch-Technische Bundesanstalt (PTB) the sensor has passed an important technical test: Spontaneous as well as stimulated magnetic fields of the brain were detected. This demonstrates the potential of the sensor for medical applications, such as, the investigation of brain currents during cognitive processes with the aim of improving neurological diagnostics. The main advantage of the new sensor developed by NIST in the USA over the conventionally used cryoelectronics is its room temperature operation capability making complicated cooling obsolete. The results have recently been published in the journal "Biomedical Optics Express".
The magnetic field sensor is called Chip-scale Atomic Magnetometer (CSAM) as it uses miniaturized optics for measuring absorption changes in a Rubidium gas cell caused by magnetic fields. The CSAM sensor was developed by NIST (National Institute of Standards and Technology), which is the national metrology institute of the USA. In this cooperation between PTB and NIST each partner contributes his own particular capabilities. PTB’s staff has long standing experience in biomagnetic measurements in a unique magnetically shielded room. NIST contributes the sensors, which are the result of a decade of dedicated research and development.
Up to now the measurement of very weak magnetic fields was the domain of cryoelectronic sensors, the so called superconducting quantum interference device (SQUID). They can be considered as the „gold standard“ for this application, but they have the disadvantage to operate only at very low temperatures close to absolute zero. This makes them expensive and less versatile compared to CSAMs. Even though at present CSAMs are still less sensitive compared to SQUIDs, measurements with a quality comparable to SQUIDs, but at lower costs, might eventually become reality. Due to the cooling requirements, SQUIDs have to be kept apart from the human body by a few centimeters. In contrast to that, CSAMs can be attached closely to the human body. This increases the signal amplitude as the magnetic field from currents inside the human bodydecays rapidly with increasing distance.
An important application is the measurement of the magnetic field distribution around the head, which is called magnetoencephalography (MEG). It enables the characterization of neuronal currents. Such investigations have gained importance during the last few years for neurologists and neuroscientists. Objective indicators of psychiatric disorders as well as age dependent brain diseases, are urgently needed for the support of today’s clinical diagnostics.
Already in 2010 scientists from NIST and PTB had successfully tested the performance of an earlier version of the present CSAM by measurements of the magnetic field of the human heart. For the present study the sensor was positioned about 4 mm away from the head of healthy subjects. At the back of the head, the magnetic fields of alpha waves were detected, a basic brain rhythm which occurs spontaneously during relaxation. In another measurement the brain fields due to the processing of tactile stimuli were identified. These fields are extremely weak and the CSAM result was validated by a simultaneous MEG measurement relying on the established SQUID technology.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=120619&CultureCode=en
Successful test at PTB of optical magnetometer with potential applications in brain imaging for neurological diagnostics and in basic research.
In future a new magnetic sensor the size of a sugar cube might simplify the measurement of brain activity. In the magnetically shielded room of Physikalisch-Technische Bundesanstalt (PTB) the sensor has passed an important technical test: Spontaneous as well as stimulated magnetic fields of the brain were detected. This demonstrates the potential of the sensor for medical applications, such as, the investigation of brain currents during cognitive processes with the aim of improving neurological diagnostics. The main advantage of the new sensor developed by NIST in the USA over the conventionally used cryoelectronics is its room temperature operation capability making complicated cooling obsolete. The results have recently been published in the journal "Biomedical Optics Express".
The magnetic field sensor is called Chip-scale Atomic Magnetometer (CSAM) as it uses miniaturized optics for measuring absorption changes in a Rubidium gas cell caused by magnetic fields. The CSAM sensor was developed by NIST (National Institute of Standards and Technology), which is the national metrology institute of the USA. In this cooperation between PTB and NIST each partner contributes his own particular capabilities. PTB’s staff has long standing experience in biomagnetic measurements in a unique magnetically shielded room. NIST contributes the sensors, which are the result of a decade of dedicated research and development.
Up to now the measurement of very weak magnetic fields was the domain of cryoelectronic sensors, the so called superconducting quantum interference device (SQUID). They can be considered as the „gold standard“ for this application, but they have the disadvantage to operate only at very low temperatures close to absolute zero. This makes them expensive and less versatile compared to CSAMs. Even though at present CSAMs are still less sensitive compared to SQUIDs, measurements with a quality comparable to SQUIDs, but at lower costs, might eventually become reality. Due to the cooling requirements, SQUIDs have to be kept apart from the human body by a few centimeters. In contrast to that, CSAMs can be attached closely to the human body. This increases the signal amplitude as the magnetic field from currents inside the human bodydecays rapidly with increasing distance.
An important application is the measurement of the magnetic field distribution around the head, which is called magnetoencephalography (MEG). It enables the characterization of neuronal currents. Such investigations have gained importance during the last few years for neurologists and neuroscientists. Objective indicators of psychiatric disorders as well as age dependent brain diseases, are urgently needed for the support of today’s clinical diagnostics.
Already in 2010 scientists from NIST and PTB had successfully tested the performance of an earlier version of the present CSAM by measurements of the magnetic field of the human heart. For the present study the sensor was positioned about 4 mm away from the head of healthy subjects. At the back of the head, the magnetic fields of alpha waves were detected, a basic brain rhythm which occurs spontaneously during relaxation. In another measurement the brain fields due to the processing of tactile stimuli were identified. These fields are extremely weak and the CSAM result was validated by a simultaneous MEG measurement relying on the established SQUID technology.
A Pilot Study in Homeopathic and Anthroposophical Treatment of Stroke
This one is impossible to figure out but homeopathy is just water so no treatment at all. Anthroposophical is defined here;
http://en.wikipedia.org/wiki/Anthroposophical_medicine
It's even more nonsensical.
A Pilot Study in Homeopathic and Anthroposophical Treatment of Stroke
You can read the full article at the link above, its bizarre.Abstract
In a retrospective pilot study with 172 patients, two complementary treatment approaches one homeopathic, the other following a WALA anthroposophic treatment were compared as to their possible efficacy in treating the sequelae of stroke. In both groups, the treatment consisted chiefly in the use of snake poisons and arnica in homeopathic doses(water). A slightly better result was found with the homeopathic approach. This practical experience made it possible to take the further step of designing a therapeutic schema that proves effective in practice while respecting both approaches the need of anthroposophical medicine for a pathophysiological rationale and the need of homeopathy for an individualized treatment.
The definition of homeopathic dilutions;
But don't take my word for any of this, ask your regular doctor, not your homeopathic, naturopathic, or integrative doctor.
If you really want to be baffled by bullshit this one is great reading;
http://www.feg.unesp.br/~ojs/index.php/ijhdr/article/viewFile/614/622
Effects of integrative medicine protocols on the improvement of neural function deficit and disability outcomes in patients with acute ischemic cerebral stroke
I would have to see the details on this before I believe Integrative medicine is useful for anything at all.
Read deconstructions of integrative medicine here; here and here.
http://www.ncbi.nlm.nih.gov/pubmed/22013790
Read deconstructions of integrative medicine here; here and here.
http://www.ncbi.nlm.nih.gov/pubmed/22013790
Abstract
OBJECTIVE:
To study the effects of integrative medicine protocols on the neural function deficit and short-term disability outcomes in patients with acute ischemic cerebral stroke.METHODS:
99 patients were randomly assigned to three groups, i.e., the Dengzhan Xixin (fleabane) group (Group A), the Kudiezi (sowthistle-leaf ixeris seedling) group (Group B), and the Western medicine control group (Group C). Dengzhan Xixin Injection was intravenously dripped to patients in Group A for 14 days. Chinese decoction was administered to them by pattern typing as well. Meanwhile, they took Dengzhan Shengmai Capsule for two months. Kudiezi Injection was intravenously dripped to patients in Group B for 14 days. Chinese decoction was administered to them by pattern typing as well. Meanwhile, they took Naoshuantong Capsule for two months. In addition to internal therapies, patients in Group A and B received acupuncture, massage, and external washing with Chinese medicine for 21 days. Patients in Group C also received modem rehabilitation therapy for 21 days, including rehabilitation training and electronic stimulus in addition to the internal medicine. The National Institute of Health Stroke Scale (NIHSS) and disability outcome (modified Rank Scale, mRS) were taken as main effect indices.RESULTS:
The NIHSS scores at each time point obviously decreased more than before treatment in all the three groups (P<0.01), but with no difference at each time point (P>0.05). The disability outcomes of all the three groups postponed as time went by. Significant difference existed among the three groups by log-lineal model (CATMOD) (P<0.05). The best effect was shown in Group B, with the markedly effective rate of 19. 35% and the total effective rate 54.84%.CONCLUSIONS:
The integrative medicine protocols could??? improve the nerve functions of ischemic stroke patients. Therefore, it could improve the disability outcomes. The comprehensive protocol (Kudiezi Injection + Naoshuantong Capsule + Chinese decoction according to pattern typing + acupuncture + massage + external washing with Chinese medicine) was better.Intravenous Ancrod for Treatment of Acute Ischemic Stroke
Snake venom if you are queasy on bat saliva. May, 2000 so where is the hyperacute protocol?
Intravenous Ancrod for Treatment of Acute Ischemic Stroke
Context
Approved treatment options for acute ischemic stroke in the United States
and Canada are limited at present to intravenous tissue-type plasminogen activator,
but bleeding complications, including intracranial hemorrhage, are a recognized
complication.
Objective To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke.
Design The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998.
Setting Forty-eight centers, primarily community hospitals, in the United States and Canada.
Patients A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis.
Interventions Patients were randomly assigned to receive ancrod (n=248) or placebo (n=252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 µmol/L.
Main Outcome Measures The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality.
Results Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (≤3 or >3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01).
Conclusion In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke.
Objective To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke.
Design The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998.
Setting Forty-eight centers, primarily community hospitals, in the United States and Canada.
Patients A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis.
Interventions Patients were randomly assigned to receive ancrod (n=248) or placebo (n=252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 µmol/L.
Main Outcome Measures The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality.
Results Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (≤3 or >3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01).
Conclusion In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke.
Ginkgo biloba after an ischaemic stroke - Chinese TCM
From the University of Maryland School of Medicine. Nothing here is very scientific.
The University of Maryland and the Center for Integrative Medicine make no warranties, express or implied, about the value or utility for any purpose of the information and resources contained herein.
http://www.compmed.umm.edu/cochrane-reviews/cochrane-rev-stroke.asp
An improvement in neurological impairment was reported with Ginkgo biloba in nine
trials that had important methodological limitations. The review authors conclude that there is no clear evidence to support the routine use of Ginkgo biloba extract to promote recovery after stroke. High-quality and large-scale randomised controlled trials are needed to test its efficacy.
The most commonly reported side effects with Ginkgo biloba are mild stomach and intestinal problems such as constipation, indigestion and diarrhoea, and headaches. Serious side effects are rare but include excessive bleeding problems. This means that people who are already taking blood thinners (anti-clotting or anticoagulant and antiplatelet medications) to prevent strokes and heart attacks should consult a doctor before taking Gingko biloba. People who have seizures are also advised to seek medical advice about using this herb.
It is likely that only people with mild strokes were included in these trials and functional ability was not measured. Ability to carry our daily activities of living are important to people as well as neurological impairments.
The University of Maryland and the Center for Integrative Medicine make no warranties, express or implied, about the value or utility for any purpose of the information and resources contained herein.
http://www.compmed.umm.edu/cochrane-reviews/cochrane-rev-stroke.asp
What the synthesised research says
One trial, which was well conducted to limit external influences on the results (biases), measured neurological deficit and did not show a clear benefit with Ginkgo biloba compared with non-active treatment (placebo). This places doubt on how beneficial Ginkgo biloba is.An improvement in neurological impairment was reported with Ginkgo biloba in nine
trials that had important methodological limitations. The review authors conclude that there is no clear evidence to support the routine use of Ginkgo biloba extract to promote recovery after stroke. High-quality and large-scale randomised controlled trials are needed to test its efficacy.
How it was tested
The researchers made a thorough search of the medical literature and found 10 controlled trials. The 792 participants in these trials received either Ginkgo biloba extract (injection or tablet), placebo, or no additional treatment with their normal supportive care. Treatment began within the first two days to some time later, or was not stated, after onset of stroke. Ginkgo biloba was given as tablets in six trials, at 120 mg to 240 mg per day for 20 to 28 days and as intravenous injections or drips over 14 to 30 days in four other trials.Side effects and general cautions
No major side effects were reported in the three trials that looked for them. Nor were adverse events evident in other identified studies that did not follow the same strict methodological design.The most commonly reported side effects with Ginkgo biloba are mild stomach and intestinal problems such as constipation, indigestion and diarrhoea, and headaches. Serious side effects are rare but include excessive bleeding problems. This means that people who are already taking blood thinners (anti-clotting or anticoagulant and antiplatelet medications) to prevent strokes and heart attacks should consult a doctor before taking Gingko biloba. People who have seizures are also advised to seek medical advice about using this herb.
It is likely that only people with mild strokes were included in these trials and functional ability was not measured. Ability to carry our daily activities of living are important to people as well as neurological impairments.
Dan Shen agents after an ischaemic stroke - Chinese TCM
From the University of Maryland School of Medicine. Nothing here is very scientific, although I did like the snake venom.
The University of Maryland and the Center for Integrative Medicine make no warranties, express or implied, about the value or utility for any purpose of the information and resources contained herein.
Dan Shen agents after an ischaemic stroke - Chinese TCM
Dan Shen agents are well accepted by Chinese doctors and they are one
of the most frequently used Chinese herbal medicines in the treatment
of acute ischaemic stroke, heart disease and major (systemic) blood flow
disorders. In stroke, the intent is to improve the local brain blood
circulation and limit the nerve and brain cell damage caused by an acute
lack of blood flow. Dan Shen agents are given as tablets or injections, often mixed with other traditional Chinese herbal medicines (as Compound Dan Shen agents). The main botanical family in Dan Shen (red sage) is Radix Salviae Miltiorrhizae. Compound Dan Shen agents also contain other Chinese herbal medicines such as Ligni dalbergiae odoriferae, Sanqi, and Bingpian to promote the curative effects and decrease the adverse effects of Dan Shen. The Compound Dan Shen dropping pill is one of these.
What the synthesised research says
Compound Dan Shen injection and Compound Dan Shen dropping pill may improve neurological impairment caused by an acute ischaemic stroke. This conclusion is based on the results of three trials that looked for an improvement in neurological deficit at the end of treatment. This is too few trials with too few participants to have a clear measure of any benefit.The methodological quality of the included trials was not scientifically rigorous enough to know whether Dan Shen agents help people with stroke and there were too few patients to draw reliable conclusions. The most important thing to people after a stroke is their ability to go about activities of daily living rather than their neurological deficits; which was not measured in these trials. The follow up was also short, approximately one month, even though spontaneous recovery does not plateau until some 5 to 6 months.
How it was tested
The researchers made a thorough search of the medical literature and found only three controlled trials with 304 acute ischaemic stroke patients. All the trials were conducted in China. The average age of patients, more men than women, was between 56 and 62 years.Two trials combined Compound Dan Shen injection with snake venom in the treatment group and only used snake venom in the control group over 28 days of treatment; all patients also received routine treatment. The doses of snake venom and Compound Dan Shen injection were 0.25 to 0.75 U and 20 ml respectively.
Oral Compound Dan Shen dropping pill was used in one study. It was given three times daily for 28 days. There was no evidence of a difference of effect between this form of Dan Shen and injection with snake venom.
The timing of the start of treatment after stroke onset was not reported. No deaths were reported within the first two weeks of treatment or during the following 21 to 28 days. This suggests the strokes were not severe.
Tuesday, May 29, 2012
Stroke risk assessment tool
Other ones here: NINDS ,Recurrence Risk Estimator , New Zealand
http://www.healthonecares.com/stroke_center/stroke-assessment.htm
Because of the prior stroke my risk according to this is high in the next 10 years. Nothing that I changed in any of the answers would change that risk.
Even changing the age down to 20 did not change the risk.
If I remove the previous stroke I am low risk. I don't trust this latest one, it doesn't have enough discriminatory power, but then according to all predictors I should have been at low risk when I did have my massive stroke.
http://www.healthonecares.com/stroke_center/stroke-assessment.htm
Because of the prior stroke my risk according to this is high in the next 10 years. Nothing that I changed in any of the answers would change that risk.
Even changing the age down to 20 did not change the risk.
If I remove the previous stroke I am low risk. I don't trust this latest one, it doesn't have enough discriminatory power, but then according to all predictors I should have been at low risk when I did have my massive stroke.
Platelet Microparticles Induce Angiogenesis and Neurogenesis after Cerebral Ischemia
Not sure exactly how one would get these microparticles.
http://www.ncbi.nlm.nih.gov/pubmed/22621230
http://www.ncbi.nlm.nih.gov/pubmed/22621230
Abstract
Activated platelets shed microparticles, which contain variety of growth factors central to angiogenesis and neurogenesis. The aim of this study was to explore whether platelet derived microparticles (PMP) can boost endogenous neural stem cells dependent repair mechanisms following stroke in a rat model. To examine the effects of PMP therapy in-vivo, we delivered PMP or vehicle via a biodegradable polymer to the brain surface after permanent middle cerebral artery occlusion (PMCAO) in rats. Rats were tested with the neurological severity score and infarct volumes were measured at 90 days post-ischemia. Immunohistochemistry was used to determine the fate of newborn cells and to count blood vessels in the ischemic brain. The results show that PMP led to a dose dependent increase in cell proliferation, neurogenesis and angiogenesis at the infarct boundary zone and significantly improved behavioral deficits.TR3-05556: Heart Repair with Human Tissue Engineered Myocardium
This is one of the California stem cell projects. This line suggests it is for stroke; $4,766,231 for Joseph Wu of Stanford to use engineered tissue patches seeded with human embryonic stem cell-derived cardiomyocytes to treat stroke. But looking at the actual grant is this title,
Recommendation: Recommended for Funding
Scientific Score: 80
Total Funds Requested $4,766,231
Award Type : Development Candidate Award
Objective and Milestones
- The objective and milestones are feasible, well planned and appropriately focused to accomplish a complex DC.
- The target product profile is scientifically reasonable and drives toward a first-in-human study to assess safety, appropriate for this stage of research. Reviewers recommended that the applicants consider into which patient population the team would advance the therapeutic candidate.
Rationale and Significance
- If successfully developed, the proposed DC could address a huge unmet clinical need in end stage heart failure, for which the prognosis is poor and treatment options are limited.
- The panel appreciated that the EHT approach addresses the rapid loss of transplanted cells, a bottleneck in development of cell therapies for the heart.
- If successfully developed, this DC will demonstrate feasibility of repairing a complex organ with an hESC-based tissue engineering strategy.
Research Project Feasibility and Design
- Reviewers were highly enthusiastic about the proposed program. The plan is logical and well-designed, and addresses all required elements to achieve a DC ready for IND-enabling studies.
- While the manufacturing and in vivo testing required to achieve this DC are technically demanding, compelling preliminary data and team expertise gave reviewers confidence that the team could successfully execute the proposed program.
- Reviewers discussed the immunological challenges of xenotransplantation in the large animal model. They strongly advised the applicants to begin in vitro testing of the selected immunosuppression regimen to ensure similar activity in both preclinical models early in the program.
- Potential immunogenicity of the DC should also be assessed.
Qualification of the PI (Co-PI and Partner PI, if applicable) and Research Team
- The panel expressed universal enthusiasm regarding the qualifications of the PI, Co-PI, Partner PI and the other members of the first rate, collaborative team.
- The budget is appropriate to support the proposed studies.
Collaborations, Assets, Resources and Environment
- Collaborations are critical to the success of the program, and reviewers valued the established collaboration with the Partner PI.
- Resources at the host institution are excellent for translational studies, including facilities and expertise for the proposed in vitro studies.
Responsiveness to the RFA
- The proposal describes a novel development candidate derived from pluripotent human cells, rendering it highly responsive to the RFA.
TR3-05556:Heart Repair with Human Tissue Engineered Myocardium with this abstract.
http://www.cirm.ca.gov/ReviewSummary_TR3-05556Recommendation: Recommended for Funding
Scientific Score: 80
Total Funds Requested $4,766,231
Award Type : Development Candidate Award
Public Abstract (provided by applicant)
Heart disease is the number one cause of morbidity and mortality in the US. With an estimated 1.5 million new or recurrent myocardial infarctions, the total economic burden on our health care system is enormous. Although conventional pharmacotherapy and surgical interventions often improve cardiac function and quality of life, many patients continue to develop refractory symptoms. Thus, the development of new therapies is urgently needed. "Tissue engineering" can be broadly defined as the application of novel bioengineering methods to understand complex structure-function relationships in normal or pathological conditions and the development of biological substitutes to restore, maintain, or improve function. It is different from "cell therapy", which is designed to improve the function of an injured tissue by simply injecting suspensions of isolated cells into the injury site. To date, two main limitations of cell therapy are (1) acute donor cell death due to unfavorable seeding environment and (2) the lack of suitable cell type that genuinely resembles human cardiac cells. Our proposal seeks to use engineered tissue patches seeded with human embryonic stem cell-derived cardiomyocytes for treatment of ischemic heart disease in small and large animal models. It represents a significant development of novel techniques to address both of the main limitations of cell therapy, and will provide a new catalyst for the entire field of stem cell-based tissue engineering.Statement of Benefit to California (provided by applicant)
Patients with end-stage heart failure have a 2-year survival rate of 25% by conventional medical therapy. Not commonly known to the public is that this dismal survival rate is actually worse when compared to patients with AIDS, liver cirrhosis, or stroke. Following a heart failure, the endogenous repair process is not sufficient to compensate for cardiomyocyte death. Thus, novel therapies with stem cells in combination with supportive scaffolds to form engineered cardiac tissue grafts is emerging as a promising therapeutic avenue. Engineered tissues have now been used to make new bladders for patients needing cystoplasty, bioarticial heart patches seeded with bone marrow cells, and more recently new trachea for patient with late stage tracheal cancer. Our multi-disciplinary team intends to push the therapeutic envelop by developing human tissue engineered myocardium for treatment of post-myocardial infarction heart failure. We will first test our engineered cardiac tissue in small and large animal models. We will perform extensive quality control measures to define morphological, molecular, and functional properties. At the end of 3 years, we are confident we will be able to derive a lead candidate that can move into IND-enabling preclinical development. These discoveries will benefit the millions of patients with heart failure in California and globally.Review
This development candidate (DC) proposal aims to evaluate an engineered heart tissue (EHT), containing human embryonic stem cell derived cardiac myocytes (hESC-CM), in preclinical models of end stage heart failure. Given that the majority of cells injected into the heart are rapidly lost, the applicants hypothesize that retaining cells using this patch-based approach will improve engraftment and heart function. The preclinical models will be assessed for cardiac function, graft retention, graft integration and safety. Additionally, the applicants will develop scaled up GMP compatible production methods, shipping standard operating procedures (SOPs), and assays to characterize materials before and after shipping. The proposal represents an international collaborative effort between individuals with expertise in stem cells, cardiac imaging, tissue engineering and cardiac surgery.Objective and Milestones
- The objective and milestones are feasible, well planned and appropriately focused to accomplish a complex DC.
- The target product profile is scientifically reasonable and drives toward a first-in-human study to assess safety, appropriate for this stage of research. Reviewers recommended that the applicants consider into which patient population the team would advance the therapeutic candidate.
Rationale and Significance
- If successfully developed, the proposed DC could address a huge unmet clinical need in end stage heart failure, for which the prognosis is poor and treatment options are limited.
- The panel appreciated that the EHT approach addresses the rapid loss of transplanted cells, a bottleneck in development of cell therapies for the heart.
- If successfully developed, this DC will demonstrate feasibility of repairing a complex organ with an hESC-based tissue engineering strategy.
Research Project Feasibility and Design
- Reviewers were highly enthusiastic about the proposed program. The plan is logical and well-designed, and addresses all required elements to achieve a DC ready for IND-enabling studies.
- While the manufacturing and in vivo testing required to achieve this DC are technically demanding, compelling preliminary data and team expertise gave reviewers confidence that the team could successfully execute the proposed program.
- Reviewers discussed the immunological challenges of xenotransplantation in the large animal model. They strongly advised the applicants to begin in vitro testing of the selected immunosuppression regimen to ensure similar activity in both preclinical models early in the program.
- Potential immunogenicity of the DC should also be assessed.
Qualification of the PI (Co-PI and Partner PI, if applicable) and Research Team
- The panel expressed universal enthusiasm regarding the qualifications of the PI, Co-PI, Partner PI and the other members of the first rate, collaborative team.
- The budget is appropriate to support the proposed studies.
Collaborations, Assets, Resources and Environment
- Collaborations are critical to the success of the program, and reviewers valued the established collaboration with the Partner PI.
- Resources at the host institution are excellent for translational studies, including facilities and expertise for the proposed in vitro studies.
Responsiveness to the RFA
- The proposal describes a novel development candidate derived from pluripotent human cells, rendering it highly responsive to the RFA.
Researchers restore neuron function to brains damaged by Huntington's disease
If one form of damage to the brain can be corrected why not stroke damage? Get your researcher working on this stuff, you do have a personal researcher don't you?
hhttp://www.eurekalert.org/pub_releases/2012-05/vari-rrn052912.php
Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models.
Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory.
In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD.
"The unique features of the iPSC approach means that the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed," said Jihwan Song, D.Phil. Associate Professor and Director of Laboratory of Developmental & Stem Cell Biology at CHA Stem Cell Institute, CHA University, Seoul, South Korea and co-author of the study.
The study, published online this week in Stem Cells, found that transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD.
Another key point in the study involves the new disease models for HD presented by this method, allowing researchers to study the underlying disease process in detail. Being able to control disease development from such an early stage, using iPS cells, may provide important clues about the very start of disease development in HD. An animal model that closely imitates the real conditions of HD also opens up new and improved opportunities for drug screening.
"Having created a model that mimics HD progression from the initial stages of the disease provides us with a unique experimental platform to study Huntington's disease pathology" said Patrik Brundin, M.D., Ph.D., Director of the Center for Neurodegenerative Science at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University, Sweden, and co-author of the study.
Huntington's disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.
hhttp://www.eurekalert.org/pub_releases/2012-05/vari-rrn052912.php
Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models.
Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory.
In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD.
"The unique features of the iPSC approach means that the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed," said Jihwan Song, D.Phil. Associate Professor and Director of Laboratory of Developmental & Stem Cell Biology at CHA Stem Cell Institute, CHA University, Seoul, South Korea and co-author of the study.
The study, published online this week in Stem Cells, found that transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD.
Another key point in the study involves the new disease models for HD presented by this method, allowing researchers to study the underlying disease process in detail. Being able to control disease development from such an early stage, using iPS cells, may provide important clues about the very start of disease development in HD. An animal model that closely imitates the real conditions of HD also opens up new and improved opportunities for drug screening.
"Having created a model that mimics HD progression from the initial stages of the disease provides us with a unique experimental platform to study Huntington's disease pathology" said Patrik Brundin, M.D., Ph.D., Director of the Center for Neurodegenerative Science at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University, Sweden, and co-author of the study.
Huntington's disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.
Monday, May 28, 2012
HOBOE (Head-of-Bed Optimization of Elevation) Study: association of higher angle with reduced cerebral blood flow velocity in acute ischemic stroke.
You can compare this one to a previous post.
current:
http://feedproxy.google.com/~r/nih/bxxu/~3/4OYCBnhlFjU/display.cgi
Cerebral autoregulation can be impaired after ischemic stroke, with potential adverse effects on cerebral blood flow during early rehabilitation.The objective of this study was to assess changes in cerebral blood flow velocity with orthostatic variation at 24 hours after stroke.This investigation was an observational study comparing mean flow velocities (MFVs) at 30, 15, and 0 degrees of elevation of the head of the bed (HOB).Eight participants underwent bilateral middle cerebral artery (MCA) transcranial Doppler monitoring during orthostatic variation at 24 hours after ischemic stroke. Computed tomography angiography separated participants into recanalized (artery completely reopened) and incompletely recanalized groups. Friedman tests were used to determine MFVs at the various HOB angles. Mann-Whitney U tests were used to compare the change in MFV (from 30� to 0�) between groups and between hemispheres within groups.For stroke-affected MCAs in the incompletely recanalized group, MFVs differed at the various HOB angles (30�: median MFV=51.5 cm/s, interquartile range [IQR]=33.0 to 103.8; 15�: median MFV=55.5 cm/s, IQR=34.0 to 117.5; 0�: median MFV=85.0 cm/s, IQR=58.8 to 127.0); there were no significant differences for other MCAs. For stroke-affected MCAs in the incompletely recanalized group, MFVs increased with a change in the HOB angle from 30 degrees to 0 degrees by a median of 26.0 cm/s (IQR=21.3 to 35.3); there were no significant changes in the recanalized group (-3.5 cm/s, IQR=-12.3 to 0.8). The changes in MFV with a change in the HOB angle from 30 degrees to 0 degrees differed between hemispheres in the incompletely recanalized group but not in the recanalized group.Generalizability was limited by sample size.The incompletely recanalized group showed changes in MFVs at various HOB angles, suggesting that cerebral blood flow in this group may be sensitive to orthostatic variation, whereas the recanalized group maintained stable blood flow velocities.
Previous:
http://oc1dean.blogspot.com/2011/11/influence-of-positioning-upon-cerebral.html
current:
http://feedproxy.google.com/~r/nih/bxxu/~3/4OYCBnhlFjU/display.cgi
Cerebral autoregulation can be impaired after ischemic stroke, with potential adverse effects on cerebral blood flow during early rehabilitation.The objective of this study was to assess changes in cerebral blood flow velocity with orthostatic variation at 24 hours after stroke.This investigation was an observational study comparing mean flow velocities (MFVs) at 30, 15, and 0 degrees of elevation of the head of the bed (HOB).Eight participants underwent bilateral middle cerebral artery (MCA) transcranial Doppler monitoring during orthostatic variation at 24 hours after ischemic stroke. Computed tomography angiography separated participants into recanalized (artery completely reopened) and incompletely recanalized groups. Friedman tests were used to determine MFVs at the various HOB angles. Mann-Whitney U tests were used to compare the change in MFV (from 30� to 0�) between groups and between hemispheres within groups.For stroke-affected MCAs in the incompletely recanalized group, MFVs differed at the various HOB angles (30�: median MFV=51.5 cm/s, interquartile range [IQR]=33.0 to 103.8; 15�: median MFV=55.5 cm/s, IQR=34.0 to 117.5; 0�: median MFV=85.0 cm/s, IQR=58.8 to 127.0); there were no significant differences for other MCAs. For stroke-affected MCAs in the incompletely recanalized group, MFVs increased with a change in the HOB angle from 30 degrees to 0 degrees by a median of 26.0 cm/s (IQR=21.3 to 35.3); there were no significant changes in the recanalized group (-3.5 cm/s, IQR=-12.3 to 0.8). The changes in MFV with a change in the HOB angle from 30 degrees to 0 degrees differed between hemispheres in the incompletely recanalized group but not in the recanalized group.Generalizability was limited by sample size.The incompletely recanalized group showed changes in MFVs at various HOB angles, suggesting that cerebral blood flow in this group may be sensitive to orthostatic variation, whereas the recanalized group maintained stable blood flow velocities.
Previous:
http://oc1dean.blogspot.com/2011/11/influence-of-positioning-upon-cerebral.html
Persistent shoulder pain in the first 6 months after stroke: results of a prospective cohort study.
The abstract doesn't tell you much.
http://www.hubmed.org/display.cgi?uids=21704795
To identify factors associated with persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke.Prospective inception cohort study.Stroke units of 2 teaching hospitals.Patients (N=31) with a clinical diagnosis of stroke.Not applicable.The development of pPSSP within the first 6 months after stroke. Clinical assessment of motor, somatosensory, cognitive, emotional, and autonomic functions, undertaken within 2 weeks (t0), at 3 months (t1), and at 6 months (t2) after stroke.Patients with pPSSP (n=9) were compared with patients without pPSSP (n=22). Bivariate logistic regression analyses showed that pPSSP was significantly associated with impaired voluntary motor control (t0, t1, t2), diminished proprioception (t0, t1), tactile extinction (t0), abnormal sensation (t1, t2), spasticity of the elbow flexor muscles (t1, t2), restricted range of motion (ROM) for both shoulder abduction (t2) and shoulder external rotation (t1, t2), trophic changes (t1), and type 2 diabetes mellitus (t0).These findings suggest a multifactorial etiology of pPSSP. The association of pPSSP with restricted, passive, pain-free ROM and signs indicative of somatosensory sensitization may implicate a vicious cycle of repetitive (micro)trauma that can establish itself rapidly after stroke. Intervention should therefore be focused on maintaining and restoring joint ROM as well as preventing injury and somatosensory sensitization. In this perspective, strategies that aim to intervene simultaneously at various levels of function can be expected to be more effective than treatment directed at merely 1 level.
http://www.hubmed.org/display.cgi?uids=21704795
To identify factors associated with persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke.Prospective inception cohort study.Stroke units of 2 teaching hospitals.Patients (N=31) with a clinical diagnosis of stroke.Not applicable.The development of pPSSP within the first 6 months after stroke. Clinical assessment of motor, somatosensory, cognitive, emotional, and autonomic functions, undertaken within 2 weeks (t0), at 3 months (t1), and at 6 months (t2) after stroke.Patients with pPSSP (n=9) were compared with patients without pPSSP (n=22). Bivariate logistic regression analyses showed that pPSSP was significantly associated with impaired voluntary motor control (t0, t1, t2), diminished proprioception (t0, t1), tactile extinction (t0), abnormal sensation (t1, t2), spasticity of the elbow flexor muscles (t1, t2), restricted range of motion (ROM) for both shoulder abduction (t2) and shoulder external rotation (t1, t2), trophic changes (t1), and type 2 diabetes mellitus (t0).These findings suggest a multifactorial etiology of pPSSP. The association of pPSSP with restricted, passive, pain-free ROM and signs indicative of somatosensory sensitization may implicate a vicious cycle of repetitive (micro)trauma that can establish itself rapidly after stroke. Intervention should therefore be focused on maintaining and restoring joint ROM as well as preventing injury and somatosensory sensitization. In this perspective, strategies that aim to intervene simultaneously at various levels of function can be expected to be more effective than treatment directed at merely 1 level.
No specific effect of whole-body vibration training in chronic stroke: a double-blind randomized controlled study.
So should I believe this one or the previous one?
current:
http://www.hubmed.org/display.cgi?uids=22289234&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+nih%2Fbxxu+%28Stroke+rehabilitation%29&utm_content=Google+Reader
To evaluate the effects of whole-body vibration (WBV) training in individuals after stroke.A double-blind randomized controlled study with assessments pre- and posttraining.A university hospital rehabilitation department.Participants (N=31; mean age � SD, 62�7 y; 6-101 mo poststroke) were randomized to an intervention group or a control group.Supervised WBV training (2 sessions/wk for 6wk; 12 repetitions of 40-60s WBV per session). The intervention group trained on a vibrating platform with a conventional amplitude (3.75 mm) and the control group on a "placebo" vibrating platform (0.2mm amplitude); the frequency was 25Hz on both platforms. All participants and examiners were blinded to the amplitudes of the 2 platforms.Primary outcome measures were isokinetic and isometric knee muscle strength (dynamometer). Secondary outcome measures were balance (Berg Balance Scale), muscle tone (Modified Ashworth Scale), gait performance (Timed Up & Go, comfortable gait speed, fast gait speed, and six-minute walk tests), and perceived participation (Stroke Impact Scale).There were no significant differences between the 2 groups after the WBV training. Significant but small improvements (P<.05) in body function and gait performance were found within both groups, but the magnitude of the changes was in the range of normative variation.Six weeks of WBV training on a vibration platform with conventional amplitude was not more efficient than a placebo vibrating platform. Therefore, the use of WBV training in individuals with chronic stroke and mild to moderate disability is not supported.
previous:
http://oc1dean.blogspot.com/2012/05/efficacy-of-whole-body-vibration.html
current:
http://www.hubmed.org/display.cgi?uids=22289234&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+nih%2Fbxxu+%28Stroke+rehabilitation%29&utm_content=Google+Reader
To evaluate the effects of whole-body vibration (WBV) training in individuals after stroke.A double-blind randomized controlled study with assessments pre- and posttraining.A university hospital rehabilitation department.Participants (N=31; mean age � SD, 62�7 y; 6-101 mo poststroke) were randomized to an intervention group or a control group.Supervised WBV training (2 sessions/wk for 6wk; 12 repetitions of 40-60s WBV per session). The intervention group trained on a vibrating platform with a conventional amplitude (3.75 mm) and the control group on a "placebo" vibrating platform (0.2mm amplitude); the frequency was 25Hz on both platforms. All participants and examiners were blinded to the amplitudes of the 2 platforms.Primary outcome measures were isokinetic and isometric knee muscle strength (dynamometer). Secondary outcome measures were balance (Berg Balance Scale), muscle tone (Modified Ashworth Scale), gait performance (Timed Up & Go, comfortable gait speed, fast gait speed, and six-minute walk tests), and perceived participation (Stroke Impact Scale).There were no significant differences between the 2 groups after the WBV training. Significant but small improvements (P<.05) in body function and gait performance were found within both groups, but the magnitude of the changes was in the range of normative variation.Six weeks of WBV training on a vibration platform with conventional amplitude was not more efficient than a placebo vibrating platform. Therefore, the use of WBV training in individuals with chronic stroke and mild to moderate disability is not supported.
previous:
http://oc1dean.blogspot.com/2012/05/efficacy-of-whole-body-vibration.html
Comparing the vibration and the
control group, we found that vibration significantly improved knee
muscle isometric strength
Haptic-Rehab: Post-Stroke Hand Rehabilitation System using Haptics
I would have loved to have something similar. My left hand is still quite worthless mainly because I have to relocate control of it someplace else and all the easy therapies like this are mainly for penumbra or bleed drainage damage.
http://www.youtube.com/watch?v=0wKdy16IFw8&feature=related
http://www.youtube.com/watch?v=0wKdy16IFw8&feature=related
Saturday, May 26, 2012
Action observation of walking/running
I wanted a central place for videos I want to keep watching to try to improve my gait. Similar to the videos I compiled for the hand. Your PT should already have made this type of stuff available to you. If you have favorites put them in the comments.
http://www.youtube.com/watch?feature=fvwp&NR=1&v=63TrmSXpH98
Running Analysis of Heel Strike versus Forefoot Strike (Same runner, 2 weeks apart)
http://www.youtube.com/watch?NR=1&feature=endscreen&v=XrOgDCZ4GUo
Best running technique ever! (Dibaba's 10K world record)
http://www.youtube.com/watch?v=Pd1QvXJS9m4&feature=endscreen
Running Muscles
http://www.youtube.com/watch?v=rflLmtUWnrA&feature=fvwp
Good Form Running
http://www.youtube.com/watch?v=Tx6x2cD6Y8Q&feature=related
Phases/Planes of Gait
http://www.youtube.com/watch?NR=1&feature=endscreen&v=_xq47GRr4Ss
Animation Reference - Female Standard Walk - Grid Overlay
http://www.youtube.com/watch?feature=endscreen&NR=1&v=G8Veye-N0A4
Animation Reference - Athletic Male Standard Walk
http://www.youtube.com/watch?feature=endscreen&NR=1&v=vq9A5FD8G5w
Walk Cycles Compilation - beginning animators, fun
http://www.youtube.com/watch?feature=endscreen&NR=1&v=k86w0zlzY54
Walk Cycle Reference 2
http://www.youtube.com/watch?NR=1&feature=endscreen&v=gNFttT5_Fjk
3D Realystic walk cycle
http://www.youtube.com/watch?v=d1-oktjC03M&feature=related
Animation Run Cycle - Extended Version
http://www.youtube.com/watch?v=2nUjWctMld4&feature=endscreen&NR=1
The Gait Cycle: A Breakdown of each Component
http://www.youtube.com/watch?v=5j4YRHf6Iyo
What not to watch;
Hemiplegic Gait
http://www.youtube.com/watch?v=ER1QHq4bvbQ&feature=related
Spastic gait in stroke patient
http://www.youtube.com/watch?v=Ice5bTjV6jw&feature=endscreen
Video Gait Analysis, watching feet from the back on a treadmill, then the side
http://www.youtube.com/watch?feature=fvwp&NR=1&v=63TrmSXpH98
Running Analysis of Heel Strike versus Forefoot Strike (Same runner, 2 weeks apart)
http://www.youtube.com/watch?NR=1&feature=endscreen&v=XrOgDCZ4GUo
Best running technique ever! (Dibaba's 10K world record)
http://www.youtube.com/watch?v=Pd1QvXJS9m4&feature=endscreen
Running Muscles
http://www.youtube.com/watch?v=rflLmtUWnrA&feature=fvwp
Good Form Running
http://www.youtube.com/watch?v=Tx6x2cD6Y8Q&feature=related
Phases/Planes of Gait
http://www.youtube.com/watch?NR=1&feature=endscreen&v=_xq47GRr4Ss
Animation Reference - Female Standard Walk - Grid Overlay
http://www.youtube.com/watch?feature=endscreen&NR=1&v=G8Veye-N0A4
Animation Reference - Athletic Male Standard Walk
http://www.youtube.com/watch?feature=endscreen&NR=1&v=vq9A5FD8G5w
Walk Cycles Compilation - beginning animators, fun
http://www.youtube.com/watch?feature=endscreen&NR=1&v=k86w0zlzY54
Walk Cycle Reference 2
http://www.youtube.com/watch?NR=1&feature=endscreen&v=gNFttT5_Fjk
3D Realystic walk cycle
http://www.youtube.com/watch?v=d1-oktjC03M&feature=related
Animation Run Cycle - Extended Version
http://www.youtube.com/watch?v=2nUjWctMld4&feature=endscreen&NR=1
The Gait Cycle: A Breakdown of each Component
http://www.youtube.com/watch?v=5j4YRHf6Iyo
What not to watch;
Hemiplegic Gait
http://www.youtube.com/watch?v=ER1QHq4bvbQ&feature=related
Spastic gait in stroke patient
http://www.youtube.com/watch?v=Ice5bTjV6jw&feature=endscreen
The Brain's Bat Signal
Mo Costandi writes on cleanup in the brain.
Microglia are the brain's resident security guards, surveilling the organ for damage and then crawling to the injury site to engulf dead neurons. Exactly how they detect problems was unclear, but researchers now show that they respond to an SOS signal from dying cells that is relayed throughout the brain. The finding may have implications for the treatment of Alzheimer's and other neurodegenerative diseases.
Rest of article here with cool video;
http://news.sciencemag.org/sciencenow/2012/05/the-brains-bat-signal.html?ref=hp
His blog here with more on injured neurons;
http://www.guardian.co.uk/science/neurophilosophy/2012/may/26/1
Microglia are the brain's resident security guards, surveilling the organ for damage and then crawling to the injury site to engulf dead neurons. Exactly how they detect problems was unclear, but researchers now show that they respond to an SOS signal from dying cells that is relayed throughout the brain. The finding may have implications for the treatment of Alzheimer's and other neurodegenerative diseases.
Rest of article here with cool video;
http://news.sciencemag.org/sciencenow/2012/05/the-brains-bat-signal.html?ref=hp
His blog here with more on injured neurons;
http://www.guardian.co.uk/science/neurophilosophy/2012/may/26/1
Neuron signalling and cockroaches
By dissecting a cockroach ... yes, live on stage ... TED Fellow and neuroscientist Greg Gage shows how brains receive and deliver electric impulses -- and how legs can respond.
Neuron signalling and cockroaches
Persistent sensory experience is good for the ageing brain
Just in case you need more proof on neuroplasticity at any age.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=120549&CultureCode=en
“This study overturns decades-old beliefs that most of the brain is hard-wired before a critical period that ends when one is a young adult,” said MPFI neuroscientist Marcel Oberlaender, PhD, first author on the paper. “By changing the nature of sensory experience, we were able to demonstrate that the brain can rewire, even at an advanced age. This may suggest that if one stops learning and experiencing new things as one ages, a substantial amount of connections within the brain may be lost.”
The researchers conducted their study by examining the brains of older rats, focusing on an area of the brain known as the thalamus, which processes and delivers information obtained from sensory organs to the cerebral cortex. Connections between the thalamus and the cortex have been thought to stop changing by early adulthood, but this was not found to be the case in the rodents studied.
Being nocturnal animals, rats mainly rely on their whiskers as active sensory organs to explore and navigate their environment. For this reason, the whisker system is an ideal model for studying whether the brain can be remodelled by changing sensory experience. By simply trimming the whiskers, and preventing the rats from receiving this important and frequent form of sensory input, the scientists sought to determine whether extensive rewiring of the connections between the thalamus and cortex would occur.
On examination, they found that the animals with trimmed whiskers had altered axons, nerve fibres along which information is conveyed from one neuron (nerve cell) to many others; those whose whiskers were not trimmed had no axonal changes. Their findings were particularly striking as the rats were considered relatively old – meaning that this rewiring can still take place at an age not previously thought possible. Also notable was that the rewiring happened rapidly – in as little as a few days.
“We’ve shown that the structure of the rodent brain is in constant flux, and that this rewiring is shaped by sensory experience and interaction with the environment,” said Oberlaender. “These changes seem to be life-long and may pertain to other sensory systems and species, including people. Our findings open the possibility of new avenues of research on development of the aging brain using quantitative anatomical studies combined with noninvasive imaging technologies suitable for humans, such as functional MRI (fMRI).”
The study was possible due to recent advances in high-resolution imaging and reconstruction techniques, developed in part by Oberlaender at MPFI. These novel methods enable researchers to automatically and reliably trace the fine and complex branching patterns of individual axons, with typical diameters less than a thousandth of a millimetre, throughout the entire brain.
Oberlaender is part of the Max Planck Florida Institute’s Digital Neuroanatomy group, led by Nobel laureate Bert Sakmann. The group focuses on the functional anatomy of circuits in the cerebral cortex that form the basis of simple behaviours (e.g. decision making). One of the group’s most significant efforts is a program dedicated to obtaining a three-dimensional map of the rodent brain. This work will provide insight into the functional architecture of entire cortical areas, and will lay the foundation for a mechanistic understanding of sensory perception and behaviour.
http://www.mpg.de/5813329/rewiring_ageing_brain
http://www.alphagalileo.org/ViewItem.aspx?ItemId=120549&CultureCode=en
“This study overturns decades-old beliefs that most of the brain is hard-wired before a critical period that ends when one is a young adult,” said MPFI neuroscientist Marcel Oberlaender, PhD, first author on the paper. “By changing the nature of sensory experience, we were able to demonstrate that the brain can rewire, even at an advanced age. This may suggest that if one stops learning and experiencing new things as one ages, a substantial amount of connections within the brain may be lost.”
The researchers conducted their study by examining the brains of older rats, focusing on an area of the brain known as the thalamus, which processes and delivers information obtained from sensory organs to the cerebral cortex. Connections between the thalamus and the cortex have been thought to stop changing by early adulthood, but this was not found to be the case in the rodents studied.
Being nocturnal animals, rats mainly rely on their whiskers as active sensory organs to explore and navigate their environment. For this reason, the whisker system is an ideal model for studying whether the brain can be remodelled by changing sensory experience. By simply trimming the whiskers, and preventing the rats from receiving this important and frequent form of sensory input, the scientists sought to determine whether extensive rewiring of the connections between the thalamus and cortex would occur.
On examination, they found that the animals with trimmed whiskers had altered axons, nerve fibres along which information is conveyed from one neuron (nerve cell) to many others; those whose whiskers were not trimmed had no axonal changes. Their findings were particularly striking as the rats were considered relatively old – meaning that this rewiring can still take place at an age not previously thought possible. Also notable was that the rewiring happened rapidly – in as little as a few days.
“We’ve shown that the structure of the rodent brain is in constant flux, and that this rewiring is shaped by sensory experience and interaction with the environment,” said Oberlaender. “These changes seem to be life-long and may pertain to other sensory systems and species, including people. Our findings open the possibility of new avenues of research on development of the aging brain using quantitative anatomical studies combined with noninvasive imaging technologies suitable for humans, such as functional MRI (fMRI).”
The study was possible due to recent advances in high-resolution imaging and reconstruction techniques, developed in part by Oberlaender at MPFI. These novel methods enable researchers to automatically and reliably trace the fine and complex branching patterns of individual axons, with typical diameters less than a thousandth of a millimetre, throughout the entire brain.
Oberlaender is part of the Max Planck Florida Institute’s Digital Neuroanatomy group, led by Nobel laureate Bert Sakmann. The group focuses on the functional anatomy of circuits in the cerebral cortex that form the basis of simple behaviours (e.g. decision making). One of the group’s most significant efforts is a program dedicated to obtaining a three-dimensional map of the rodent brain. This work will provide insight into the functional architecture of entire cortical areas, and will lay the foundation for a mechanistic understanding of sensory perception and behaviour.
http://www.mpg.de/5813329/rewiring_ageing_brain
Cleveland firm invents a patch that fights shoulder pain
The title is misleading, reducing pain is the side effect of direct eStim of the shoulder muscles.
http://www.cleveland.com/healthfit/index.ssf/2012/05/cleveland_firm_invents_a_patch.html
Shoulder pain after suffering a stroke is no small thing.
That pain -- the most common kind resulting from a stroke -- can prevent a patient from doing the rehabilitation they need to improve mobility. It also can be the beginning of a devastating downward spiral of incapacitation.
For such patients, a new device called the Smartpatch, created by Highland Heights-based SPR Therapeutics, might eventually be what turns that scenario around. The product will enter its third and final clinical trial within the next six months, before applying for FDA clearance. In Europe, the process is further along: approval for the Smartpatch is anticipated by this fall.
Maria Bennett, president and CEO of SPR, helped develop this innovation in pain treatment while working with her former adviser and mentor, Dr. John Chae. Chae is the director of rehabilitation research and stroke rehabilitation at the MetroHealth Rehabilitation Institute of Ohio.
Medical professionals have long used electrical stimulation in attempts to restore body function -- for example, in the case of spinal cord injuries, explains Bennett, 38, who has a master's degree in biomedical engineering from Case Western Reserve University. So initially, the thought was to create a device that stimulated muscles in a paralyzed shoulder.
The rest at the link.
http://www.cleveland.com/healthfit/index.ssf/2012/05/cleveland_firm_invents_a_patch.html
Shoulder pain after suffering a stroke is no small thing.
That pain -- the most common kind resulting from a stroke -- can prevent a patient from doing the rehabilitation they need to improve mobility. It also can be the beginning of a devastating downward spiral of incapacitation.
For such patients, a new device called the Smartpatch, created by Highland Heights-based SPR Therapeutics, might eventually be what turns that scenario around. The product will enter its third and final clinical trial within the next six months, before applying for FDA clearance. In Europe, the process is further along: approval for the Smartpatch is anticipated by this fall.
Maria Bennett, president and CEO of SPR, helped develop this innovation in pain treatment while working with her former adviser and mentor, Dr. John Chae. Chae is the director of rehabilitation research and stroke rehabilitation at the MetroHealth Rehabilitation Institute of Ohio.
Medical professionals have long used electrical stimulation in attempts to restore body function -- for example, in the case of spinal cord injuries, explains Bennett, 38, who has a master's degree in biomedical engineering from Case Western Reserve University. So initially, the thought was to create a device that stimulated muscles in a paralyzed shoulder.
The rest at the link.
Training the Brain Could Help Reduce Pain
Another use for neuroplasticity.
http://www.sciencedaily.com/releases/2012/05/120517131701.htm
Training the brain to reduce pain could be a promising approach for treating phantom limb pain and complex regional pain syndrome, according to an internationally known neuroscience researcher speaking May 17 at the American Pain Society's Annual Scientific Meeting.
G. Lorimer Moseley, PhD, professor of clinical neurosciences at
University of South Australia and Neuroscience Research Australia, and
head of the Body in Mind research team, told the plenary session
audience that the brain stores maps of the body that are integrated with
neurological systems that survey, regulate, and protect the integrity
of the body physically and psychologically. These cortical maps govern
movement, sensation and perception, and there is growing evidence,
according to Moseley, showing that disruptions of brain maps occur in
people with chronic pain. The best evidence is from those with phantom
limb pain and complex regional pain syndrome, but there is also data
from chronic back pain.
Moseley's research is focused on the role of the brain and mind in chronic and complex pain disorders. Through collaborations with clinicians, scientists and patients, the Body in Mind team is exploring how the brain and its representation of the body change when pain persists, how the mind influences physiological regulation of the body, how the changes in the brain and mind can be normalized with treatment.
"We're learning that chronic pain is associated with disruption of brain maps of the body and of the space around the body. When the brain determines the location of a sensory event, it integrates the location of the event in the body with a map of space. Disruption of these processes might be contributing to the problem," said Moseley. He added that it is possible for the body to be unharmed but the brain will respond by causing pain because it misinterpreted a benign stimulus as an attack. "We want to gradually train the brain to stop trying to protect body tissue that doesn't need protecting."
Moseley said the brain can "rewire" itself, a process called neuroplasticity. Often painful stimuli triggered by a broken bone or other trauma cause the brain to rewire and, as a result, the damage signal is never switched off after the initial body trauma is resolved. The result: Chronic pain. So if the brain is capable of changing to cause persistent pain, can it be changed back to normal to alleviate pain?
"The brain is the focal point of the pain experience, but the plasticity phenomena can be harnessed to help alleviate pain," Moseley said.
He further stated that disrupted cortical body maps may contribute to the development or maintenance of chronic pain and, therefore, could be viable targets for treatment. One treatment approach involves targeting motor systems through a process Moseley calls graded motor imagery. It relies on using visual images to help the brain change its perceptions of the body after prolonged pain stimuli. "For someone with phantom limb pain, the brain's body map still includes the severed arm or leg, and without any real stimuli from the region, it continues to produce pain," Moseley explained.
He reported that studies with graded motor imagery have shown encouraging results in complex regional pain syndrome and in phantom limb pain.
"Our work shows that the complex neural connections in the brain not only are associated with chronic pain, they can be reconnected or manipulated through therapy that alters brain perceptions and produce pain relief," said Moseley.
American Pain Society (2012, May 17). Training the brain could help reduce pain. ScienceDaily. Retrieved May 26, 2012, from http://www.sciencedaily.com /releases/2012/05/120517131701.htm
http://www.sciencedaily.com/releases/2012/05/120517131701.htm
Training the brain to reduce pain could be a promising approach for treating phantom limb pain and complex regional pain syndrome, according to an internationally known neuroscience researcher speaking May 17 at the American Pain Society's Annual Scientific Meeting.
Moseley's research is focused on the role of the brain and mind in chronic and complex pain disorders. Through collaborations with clinicians, scientists and patients, the Body in Mind team is exploring how the brain and its representation of the body change when pain persists, how the mind influences physiological regulation of the body, how the changes in the brain and mind can be normalized with treatment.
"We're learning that chronic pain is associated with disruption of brain maps of the body and of the space around the body. When the brain determines the location of a sensory event, it integrates the location of the event in the body with a map of space. Disruption of these processes might be contributing to the problem," said Moseley. He added that it is possible for the body to be unharmed but the brain will respond by causing pain because it misinterpreted a benign stimulus as an attack. "We want to gradually train the brain to stop trying to protect body tissue that doesn't need protecting."
Moseley said the brain can "rewire" itself, a process called neuroplasticity. Often painful stimuli triggered by a broken bone or other trauma cause the brain to rewire and, as a result, the damage signal is never switched off after the initial body trauma is resolved. The result: Chronic pain. So if the brain is capable of changing to cause persistent pain, can it be changed back to normal to alleviate pain?
"The brain is the focal point of the pain experience, but the plasticity phenomena can be harnessed to help alleviate pain," Moseley said.
He further stated that disrupted cortical body maps may contribute to the development or maintenance of chronic pain and, therefore, could be viable targets for treatment. One treatment approach involves targeting motor systems through a process Moseley calls graded motor imagery. It relies on using visual images to help the brain change its perceptions of the body after prolonged pain stimuli. "For someone with phantom limb pain, the brain's body map still includes the severed arm or leg, and without any real stimuli from the region, it continues to produce pain," Moseley explained.
He reported that studies with graded motor imagery have shown encouraging results in complex regional pain syndrome and in phantom limb pain.
"Our work shows that the complex neural connections in the brain not only are associated with chronic pain, they can be reconnected or manipulated through therapy that alters brain perceptions and produce pain relief," said Moseley.
American Pain Society (2012, May 17). Training the brain could help reduce pain. ScienceDaily. Retrieved May 26, 2012, from http://www.sciencedaily.com /releases/2012/05/120517131701.htm
New Stem Cell Method: Hope for Heart Failure Patients?
If heart researchers can do this our even smarter brain researchers should be able to follow. We already have astrocytes in a lab dish and brain-in-a-dish. There is also artificial nerves and the University of Wisconsin already has
The heart abstract here:
A writeup here; easier to understand;
Brain Science Podcast - Brain Wiring Dr. Seung
Connectome knowledge with , I posted about him earlier. He has a new book out- Connectome. This is something all our researchers need to know if they hope to fix broken connections.
Dr. Sebastian Seung (MIT) is an ambitious young scientist; his goal is to unravel the entire wiring diagram of the human brain. Considering that it took over a decade to determine the wiring diagram for the roundworm C elegans, which has a mere 302 neurons, it is clear that scientists can't leap directly to the 80 billion neuron human brain. Even so, in his new book Connectome: How the Brain's Wiring Makes Us Who We Are, Seung makes a very good argument for the value of this long term project. In Episode 85 of the Brain Science Podcast Ginger Campbell MD talked with Dr. Seung both about the challenges and potential benefits of this work.
http://traffic.libsyn.com/brainsciencepodcast/BSP_85-Seung.mp3
transcript here, hopefully the file is not corrupted anymore.
http://www.brainsciencepodcast.com/storage/transcripts/year-6/85-brainscience-Seung.pdf
Dr. Sebastian Seung (MIT) is an ambitious young scientist; his goal is to unravel the entire wiring diagram of the human brain. Considering that it took over a decade to determine the wiring diagram for the roundworm C elegans, which has a mere 302 neurons, it is clear that scientists can't leap directly to the 80 billion neuron human brain. Even so, in his new book Connectome: How the Brain's Wiring Makes Us Who We Are, Seung makes a very good argument for the value of this long term project. In Episode 85 of the Brain Science Podcast Ginger Campbell MD talked with Dr. Seung both about the challenges and potential benefits of this work.
http://traffic.libsyn.com/brainsciencepodcast/BSP_85-Seung.mp3
transcript here, hopefully the file is not corrupted anymore.
http://www.brainsciencepodcast.com/storage/transcripts/year-6/85-brainscience-Seung.pdf
THERAPEUTIC EXERCISE and Range of Motion ROM Exercises
From a PT site, great definitions and one diagram. Just in case your therapist isn't explaining this to you.
http://pt-rehabilitation.com/2012/04/therapeutic-exercise-and-range-of-motion-rom-exercises.html
http://pt-rehabilitation.com/2012/04/therapeutic-exercise-and-range-of-motion-rom-exercises.html
Friday, May 25, 2012
Glenohumeral subluxation in hemiplegia: An overview
In case this is one of your problems, they do talk a bit about shoulder pain which was one of my problems although my shoulder never subluxed.
This has nothing to do with chiropractic subluxation.
http://www.rehab.research.va.gov/jour/05/42/4/pdf/paci.pdf
The shoulder complex consists of four separate joints,
which afford it incredible mobility in all planes of motion,
but at the expense of its stability. The glenohumeral joint
(GHJ) relies on the integrity of muscular and capsuloligamentous
structures rather than bony conformation for its
stability [1]. Injury or paralysis of muscles around the
shoulder complex may lead to GHJ subluxation. Glenohumeral
subluxation (GHS), a frequent complication for
patients with a poststroke hemiplegia, is reported to be
present in 17 to 81 percent of patients with hemiplegia
following stroke [2], However, GHS’s role in poststroke
complications is still controversial. Although the impact
of GHS on the development of shoulder pain (SP) and
upper-limb functional recovery has not been completely
explained, a number of authors [2–6] consider GHS an
important source of SP. Moreover, several recent reviews
focused on SP describe GHS management as the main
intervention to prevent SP [2,5–6]. Thus, although GHS is
probably the most cited problem causing shoulder complications
after stroke, no paper is available that focuses
directly on this problem and describes in detail the main
aspects of the origin, assessment, or treatment of this frequent
and poorly understood complication.
This paper intends to—
• provide an extensive overview on GHS,
• help explain its role in poststroke complications,
• report the reliability and validity of clinical evaluations,
and
• summarize the effectiveness studies on its prevention
and management.
Rest at the link.
This has nothing to do with chiropractic subluxation.
http://www.rehab.research.va.gov/jour/05/42/4/pdf/paci.pdf
The shoulder complex consists of four separate joints,
which afford it incredible mobility in all planes of motion,
but at the expense of its stability. The glenohumeral joint
(GHJ) relies on the integrity of muscular and capsuloligamentous
structures rather than bony conformation for its
stability [1]. Injury or paralysis of muscles around the
shoulder complex may lead to GHJ subluxation. Glenohumeral
subluxation (GHS), a frequent complication for
patients with a poststroke hemiplegia, is reported to be
present in 17 to 81 percent of patients with hemiplegia
following stroke [2], However, GHS’s role in poststroke
complications is still controversial. Although the impact
of GHS on the development of shoulder pain (SP) and
upper-limb functional recovery has not been completely
explained, a number of authors [2–6] consider GHS an
important source of SP. Moreover, several recent reviews
focused on SP describe GHS management as the main
intervention to prevent SP [2,5–6]. Thus, although GHS is
probably the most cited problem causing shoulder complications
after stroke, no paper is available that focuses
directly on this problem and describes in detail the main
aspects of the origin, assessment, or treatment of this frequent
and poorly understood complication.
This paper intends to—
• provide an extensive overview on GHS,
• help explain its role in poststroke complications,
• report the reliability and validity of clinical evaluations,
and
• summarize the effectiveness studies on its prevention
and management.
Rest at the link.
Chemokines in CNS injury and repair
Maybe a different way to look at the neuronal cascade of death.
http://www.springerlink.com/content/63072246572u47q4/
http://www.springerlink.com/content/63072246572u47q4/
Abstract
Recruitment
of inflammatory cells is known to drive the secondary damage cascades
that are common to injuries of the central
nervous system (CNS). Cell activation and infiltration to
the injury site is orchestrated by changes in the expression of
chemokines, the chemoattractive cytokines. Reducing the
numbers of recruited inflammatory cells by the blocking of the action
of chemokines has turned out be a promising approach to
diminish neuroinflammation and to improve tissue preservation and
neovascularization. In addition, several chemokines have
been shown to be essential for stem/progenitor cell attraction, their
survival, differentiation and cytokine production. Thus,
chemokines might indirectly participate in remyelination,
neovascularization
and neuroprotection, which are important prerequisites for
CNS repair after trauma. Moreover, CXCL12 promotes neurite outgrowth
in the presence of growth inhibitory CNS myelin and enhances
axonal sprouting after spinal cord injury (SCI). Here, we review
current knowledge about the exciting functions of chemokines
in CNS trauma, including SCI, traumatic brain injury and stroke.
We identify common principles of chemokine action and
discuss the potentials and challenges of therapeutic interventions with
chemokines.
Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial
From the Lancet;
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960724-7/abstract
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960724-7/abstract
Summary
Background
Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.
Methods
We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4—5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).
Findings
1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85—1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86—1·08).
Interpretation
Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
Background
Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.
Methods
We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4—5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).
Findings
1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85—1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86—1·08).
Interpretation
Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
Math predicts size of clot-forming cells
Lets get these persons involved with stroke prevention researchers and see what ideas they come up with on prevention.
http://www.eurekalert.org/pub_releases/2012-05/uoc--mps052512.php
UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better understanding of how they form and behave could have wide implications.
"Platelet size has to be very specific for blood clotting," said Alex Mogilner, professor of mathematics, and neurobiology, physiology and behavior at UC Davis and a co-author of the paper, published this week in the journal Nature Communications. "It's a longstanding puzzle in platelet formation, and this is the first quantitative solution."
Mogilner and UC Davis postdoctoral scholars Jie Zhu and Kun-Chun Lee developed a mathematical model of the forces inside the cells that turn into platelets, accurately predicting their final size and shape.
They were collaborating with a team led by Joseph Italiano and Jonathon Thon at Harvard Medical School and Brigham and Women's Hospital, Boston.
Platelets are made by bone marrow cells called megakaryocytes. They bud off first as large, circular pre-platelets, form into a dumbbell-shaped pro-platelet, then finally divide into a standard-sized, disc-shaped platelet. A typical person has about a trillion platelets in circulation at a time, and makes about 100 billion new platelets a day, each living for 8 to 10 days.
Inside the pre- and pro-platelets is a ring of protein microtubules, which exerts pressure to straighten and broaden the nascent cells. But overlying the ring is a rigid cortex of proteins that prevents the platelets from expanding.
By tweaking the number of microtubules in the bundles, Mogilner, Zhu and Lee found that they could correctly predict how pro-platelets would flip into a dumbbell shape, as well as the size and shape of mature platelets.
http://www.eurekalert.org/pub_releases/2012-05/uoc--mps052512.php
UC Davis mathematicians have helped biologists figure out why platelets, the cells that form blood clots, are the size and shape that they are. Because platelets are important both for healing wounds and in strokes and other conditions, a better understanding of how they form and behave could have wide implications.
"Platelet size has to be very specific for blood clotting," said Alex Mogilner, professor of mathematics, and neurobiology, physiology and behavior at UC Davis and a co-author of the paper, published this week in the journal Nature Communications. "It's a longstanding puzzle in platelet formation, and this is the first quantitative solution."
Mogilner and UC Davis postdoctoral scholars Jie Zhu and Kun-Chun Lee developed a mathematical model of the forces inside the cells that turn into platelets, accurately predicting their final size and shape.
They were collaborating with a team led by Joseph Italiano and Jonathon Thon at Harvard Medical School and Brigham and Women's Hospital, Boston.
Platelets are made by bone marrow cells called megakaryocytes. They bud off first as large, circular pre-platelets, form into a dumbbell-shaped pro-platelet, then finally divide into a standard-sized, disc-shaped platelet. A typical person has about a trillion platelets in circulation at a time, and makes about 100 billion new platelets a day, each living for 8 to 10 days.
Inside the pre- and pro-platelets is a ring of protein microtubules, which exerts pressure to straighten and broaden the nascent cells. But overlying the ring is a rigid cortex of proteins that prevents the platelets from expanding.
By tweaking the number of microtubules in the bundles, Mogilner, Zhu and Lee found that they could correctly predict how pro-platelets would flip into a dumbbell shape, as well as the size and shape of mature platelets.
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