Deans' stroke musings

Beer bottling stroke rehab

2012-03-04T00:40:00.007-06:00

I brewed some Irish Draught Ale a couple of months ago and today decided to bottle it by myself(48 bottles). This was quite the challenge since I usually invite a friend over to cap the bottles in return for some of the beer. I have a two-handed capper like this. Keeping the cap in place while I pry my hand onto one of the levers involves picking the cap up several times. I can't get my wrist to unlock from spasticity so I could never get my upper body weight over the levers to properly crimp the cap. Luckily I only knocked over one bottle. I ended up putting the bottle in one of the slots in a wooden soda case and used my teeth/mouth on one of the levers to get about 15 bottles capped. Then my wife and daughter came home and I got them to finish the capping for me. I try to do this when they are out because both of them dislike the smell or taste of beer. If I continue this I'll have to get a single arm capper like this. I had a homebrewed coffee stout to celebrate this evening.

wooden soda case above, bench capper below

Scalp Acupuncture Fights Dementia – New Research

2012-03-03T15:02:00.004-06:00

Comparing scalp acupuncture to regular acupuncture is not any type of valid research. I would love to have scientifically explained why acupuncture works and not just a placebo.
http://www.healthcmi.com/index.php/acupuncturist-news-online/502-scalpacupuncturefightsdementia

Researchers(where is the research paper?) conclude that acupuncture is beneficial for the treatment of vascular dementia. Vascular dementia is caused by brain damage due to impaired blood flow to the brain. This is common after a stroke or a series of mini-strokes. Any condition that damages blood vessels that feed oxygen and nutrients to the brain may cause vascular dementia.

The study compared scalp acupuncture with standard body acupuncture. In this multi-center randomized controlled clinical trial, 184 subjects with vascular dementia due to Liver and Kidney deficiency received either scalp acupuncture or body acupuncture. The scalp acupuncture group showed significantly greater improvements in cognition than the body style acupuncture group. Social behavior scores improved significantly in both hthe body style and scalp acupuncture groups. TCM (Traditional Chinese Medicine) differential diagnostic conditions improved significantly in both acupuncture groups as did the ADL (Activities of Daily Living) score. Overall, scalp acupuncture received higher improvement scores due to its ability to improve cognition. The researchers concluded that scalp acupuncture substantially improves the overall condition of patients with vascular dementia including cognition, activities of daily living, TCM signs and symptoms, mental state and social behavior.

Mirror neurons

2012-03-03T11:47:00.001-06:00

Something we may be able to use to recover.
For a simple, entertaining explanation from the Nova science series, watch this brief video. Transcript provided if you don't want to watch.

Nanotechnology to repair the brain

2012-03-03T11:37:00.002-06:00

These people are after my heart. Better understanding of how the brain works before we can attempt to repair it and nanotechnology. It may be from 2008 but it needs more exposure so more researchers work on this stuff.
http://www.nanowerk.com/spotlight/spotid=8760.php

Neural engineering is an emerging discipline that uses engineering techniques to investigate the function and manipulate the behavior of the central or peripheral nervous systems. Neural engineering is highly interdisciplinary and relies on expertise from computational neuroscience, experimental neuroscience, clinical neurology, electrical engineering and signal processing of living neural tissue, and encompasses elements from robotics, computer engineering, neural tissue engineering, materials science, and nanotechnology.
In order for neural prostheses to augment or restore damaged or lost functions of the nervous system they need to be able to perform two main functions: stimulate the nervous system and record its activity. To do that, neural engineers have to gain a full understanding of the fundamental mechanisms and subtleties of cell-to-cell signaling via synaptic transmission, and then develop the technologies to replicate these mechanisms with artificial devices and interface them to the neural system at the cellular level. A group of European researchers has now shown that carbon nanotubes may become the ideal material for repairing damaged brain tissue.
"Our findings show that carbon nanotubes, which, like the nervous cells of our brain, are excellent electrical signal conductors and form intimate mechanical contacts with cellular membranes, thereby establishing a functional link to neuronal structures," Laura Ballerini, a professor of physiology, together with Maurizio Prato, professor of organic chemistry, both at the University of Trieste, Italy, explain to Nanowerk. "Such a functional and mechanical link might favor electrical shortcuts between the proximal and distal compartments of the neuron, therefore improving neuronal performance."
The study was conducted in Prato's and Ballerini's laboratories at the University of Trieste, Italy, in collaboration with Henry Markram's Laboratory of Neural Microcircuitry at Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland, and Michel Giugliano (now an assistant professor at the University of Antwerp). The team has published their findings in the December 21, 2008 online edition of Nature Nanotechnology ("Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts").
These findings represent one of the earliest attempts at linking electrical phenomena in nanomaterials to neuronal excitability.
For their experiments, the team deposited single-wall or multi-wall carbon nanotubes on a glass substrate and subsequently defunctionalized them by thermal treatment to form glass slides covered with a purified and mechanically stable thin film of about 50-70 nm thickness. This dense network of nanotubes acts as a largely resistive network that permits long-range electrical connectivity.
The effect of nanotubes on neuronal integrative properties was then investigated by comparing the electrophysiology of rat hippocampal cells cultured on control substrates to those grown on a thin film of purified nanotubes for 8 to 12 days.

TSEM micrograph of a cultured rat hippocampal neuron grown on a layer of purified carbon nanotubes. (Image: Laura Ballerini, University of Trieste)
"In a sample of cultures grown on nanotubes we quantified – in terms of postsynaptic currents frequency – the presence of a significant increase in synaptic activity, compared to control cultures," says Ballerini. "This increased activity represents a typical feature of neurons grown on nanotube substrates."
During the last few years, several research groups supported the use of carbon nanotubes substrates as potential biocompatible materials that promote cell attachment, differentiation, growth and long term neuronal survival.
Ballerini and Giugliano, together with their colleagues at the University of Trieste and the Brain Mind Institute at EPFL, have been working on interfacing neurons with carbon nanotubes for a while now and we have reported on some of their earlier findings in a previous Nanowerk Spotlight ("Nanotechnology coming to a brain near you").
In this previous work, they reported, for the first time, the effects of carbon nanotubes substrates on the electrical behavior of neuronal networks in vitro.
Ballerini notes that the growth of functional brain circuits on a conductive carbon nanotubes meshwork was always accompanied by powerful physiological changes, in the form of a significant enhancement in the efficacy of neural signal transmission, suggesting that the electrical conductivity of the carbon nanotube-substrate might be underlying these physiological effects. "Yet, the specific functional mechanisms leading to carbon nanotubes-driven neuronal potentiation were largely unexplored," she says.
This new work now considerably widens the perspectives of employing conductive nanomaterials for neuroengineering applications. It proposes carbon nanotubes not only as ideal probes for bidirectional interfaces in neuroprosthetics but also as nanotools to endogenously (re)engineer single-neuron excitability and network connectivity.
"Our results are extremely relevant for the emerging field of neuro-engineering and neuroprosthetics," explains Giugliano, who hypothesizes that the nanotubes could be used as a new building block of novel "electrical bypass" systems for treating traumatic injury of the central nervous system. "Carbon nanotube electrodes could also be used to replace metal parts in clinical applications such as deep brain stimulation for the treatment of Parkinson's disease or severe depression. And they show promise as a whole new class of smart materials for use in a wide range of potential neuroprosthetic applications."
Markram, who heads of the Laboratory of Neural Microcircuitry and an author on the paper, adds: "There are three fundamental obstacles to developing reliable neuroprosthetics: 1) stable interfacing of electromechanical devices with neural tissue, 2) understanding how to stimulate the neural tissue, and 3) understanding what signals to record from the neurons in order for the device to make an automatic and appropriate decision to stimulate. The new carbon nanotube-based interface technology discovered together with state of the art simulations of brain-machine interfaces is the key to developing all types of neuroprosthetics – sight, sound, smell, motion, vetoing epileptic attacks, spinal bypasses, as well as repairing and even enhancing cognitive functions."

AtriCure gets FDA nod for stroke safety and feasibility trial

2012-03-02T16:27:00.004-06:00

I think this is for afib but they didn't show a device or explain it in laymans terms.
http://www.medcitynews.com/2012/03/atricure-gets-fda-nod-for-stroke-safety-and-feasibility-trial/?utm_source=rss&utm_medium=rss&utm_campaign=atricure-gets-fda-nod-for-stroke-safety-and-feasibility-trial

This might be it.

Cardiology medical device company AtriCure (NASDAQ:ATRC) has received U.S. Food and Drug Administration approval for a stroke safety and feasibility trial of its AtriClip device.

The trial will enroll up to 30 patients at six sites and begin enrollment in the second half of 2012, CEO Dave Drachman said earlier this week in a conference call with analysts.The Cincinnati-area company is hoping to obtain a label from the FDA for the AtriClip to be used in standalone procedures that involve exclusion of the left atrial appendage, a thumb-sized pouch on top of the left side of the heart from which blood clots that cause strokes often originate.

The feasibility study is part of the beginning of the process, however. AtriCure doesn’t expect to receive the new label for the AtriClip for several years, chief financial officer Julie Piton said in December.

Here’s how Drachman described the push to obtain the label during the call:

The aim of this project is to start the process of demonstrating that the AtriClip system reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for whom long-term oral coagulation — anticoagulation therapy — is currently indicated.

AtriCure is also working on a new version of the AtriClip device that could be used in standalone thoracoscopic procedures, which involve inserting a a narrow tube with a camera through a small incision in the chest wall. The existing version of the device is cleared in the U.S. only for use in conjunction with other open-cardiac surgical procedures in which the physician has direct visualization.

AtriCure plans later this year to submit a 510(k) application for the new AtriClip platform, Drachman said.

Duration of Diabetes Raises Stroke Risk

2012-03-02T13:32:00.001-06:00

One thing I don't have to worry about.
http://www.medpagetoday.com/Cardiology/Strokes/31445?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=03-02-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=

The risk of ischemic stroke increased by 3% for each additional year a patient had diabetes, researchers found.

Compared with nondiabetics in the longitudinal study, those who had the disease for at least 10 years had a threefold higher stroke risk (HR 3.2, 95% CI 2.4 to 4.5), Mitchell Elkind, MD, of Columbia University in New York City, and colleagues reported online in Stroke: Journal of the American Heart Association.

Although stroke rates have been dropping among diabetics, more people are developing the disease -- and at younger ages -- because of the obesity epidemic. That means that the stroke burden is growing heavier, particularly as the population ages and people live longer.

"It is thus important to better understand the dynamics between diabetes, time, and stroke, and to emphasize the importance of interventions to prevent early diabetes," the authors wrote. "Minimizing the number of years a patient has diabetes would help combat the increase in stroke risk with each year of the disease."

Elkind and colleagues examined data from 3,298 individuals participating in the Northern Manhattan Study who had never been diagnosed with a stroke. The average age was 69. Half of the participants were Hispanic, 21% were white, and 24% were black.

About one-fifth (22%) had diabetes at baseline and another 10% reported new-onset diabetes during an average follow-up of nine years.

There were 244 ischemic strokes recorded during the study.

After adjustment for demographics and cardiovascular risk factors, ischemic stroke was predicted by the presence of baseline diabetes (HR 2.5, 95% CI 1.9 to 3.3) and diabetes as a time-dependent variable (HR 2.4, 95% CI 1.8 to 3.2), which takes into account the development of diabetes during follow-up.

The researchers had hypothesized that incorporating incident diabetes would change the magnitude of the association, but it did not, possibly because these older individuals already had a high cardiovascular risk burden at baseline that did not change much with the development of diabetes.

Other possible reasons incident diabetes did not improve risk prediction included greater compliance with therapy among those newly diagnosed, a shorter duration of diabetes among the incident cases, which might not be long enough to translate into a higher stroke risk, and the potential for missing cases during follow-up because of the use of self-report.

Compared with nondiabetics, the risk of ischemic stroke was similar for those who had diabetes for up to five years (HR 1.7) and those who had the disease for five to 10 years (HR 1.8). The risk was greater for those who had diabetes for a decade or more (HR 3.2).

The growing stroke risk that accompanies a longer duration of diabetes could be mediated through several mechanisms, according to the researchers:

Greater carotid plaque thickness
Accelerated microvascular and macrovascular complications from long-term hypertension
Greater risk of microalbuminuria, which has been shown to be a risk factor for stroke in patients with diabetes
Endothelial dysfunction
Abnormalities in fibrinogen and clotting mechanisms

The finding "warrants steps to institute long-standing and sustainable lifestyle changes for primary prevention and appropriate long-term management after diagnosis," the authors wrote.

They acknowledged some limitations of the study, including the lack of information on fasting blood glucose and glycated hemoglobin during follow-up and possible confounding of the association between diabetes duration and stroke risk by age.

Plan experiments, track progress, get results.

2012-03-02T09:37:00.002-06:00

No excuses for anyone that they can't do research.
ER doctors, physiatrists, neurologists, nurses, OTs, PTs, STs, patients,caregivers, stroke associations
http://www.labguru.com/

STROKE IS NOT INCREASED BY CHIROPRACTIC

2012-03-01T23:58:00.003-06:00

You'll have to decide for yourself if you can believe this.
The chiropractor one here:
http://www.ronhayter.com/health-and-fitness/stroke-is-not-increased-by-chiropractic/
I'm a false mind I guess.
Other scientific results here:
http://oc1dean.blogspot.com/2011/12/chiropractic-stroke.html
My opinion only, I will never get my neck adjusted.

New high definition fiber tracking reveals damage caused by traumatic brain injury, Pitt team finds

2012-03-01T23:43:00.002-06:00

So lets start using this for strokes, anything to actually get a real damage diagnosis.
http://www.eurekalert.org/pub_releases/2012-03/uops-nhd030112.php
A powerful new imaging technique called High Definition Fiber Tracking (HDFT) will allow doctors to clearly see for the first time neural connections broken by traumatic brain injury (TBI) and other disorders, much like X-rays show a fractured bone, according to researchers from the University of Pittsburgh in a report published online today in the Journal of Neurosurgery.

In the report, the researchers describe the case of a 32-year-old man who wasn't wearing a helmet when his all-terrain vehicle crashed. Initially, his CT scans showed bleeding and swelling on the right side of the brain, which controls left-sided body movement. A week later, while the man was still in a coma, a conventional MRI scan showed brain bruising and swelling in the same area. When he awoke three weeks later, the man couldn't move his left leg, arm and hand.

"There are about 1.7 million cases of TBI in the country each year, and all too often conventional scans show no injury or show improvement over time even though the patient continues to struggle," said co-senior author and UPMC neurosurgeon David O. Okonkwo, M.D., Ph.D., associate professor, Department of Neurological Surgery, Pitt School of Medicine. "Until now, we have had no objective way of identifying how the injury damaged the patient's brain tissue, predicting how the patient would fare, or planning rehabilitation to maximize the recovery."

HDFT might be able to provide those answers, said co-senior author Walter Schneider, Ph.D., professor of psychology at Pitt's Learning Research and Development Center (LRDC), who led the team that developed the technology. Data from sophisticated MRI scanners is processed through computer algorithms to reveal the wiring of the brain in vivid detail and to pinpoint breaks in the cables, called fiber tracts. Each tract contains millions of neuronal connections.

"In our experiments, HDFT has been able to identify disruptions in neural pathways with a clarity that no other method can see," Dr. Schneider said. "With it, we can virtually dissect 40 major fiber tracts in the brain to find damaged areas and quantify the proportion of fibers lost relative to the uninjured side of the brain or to the brains of healthy individuals. Now, we can clearly see breaks and identify which parts of the brain have lost connections."

HDFT scans of the study patient's brain were performed four and 10 months after he was injured; he also had another scan performed with current state-of the-art diffusion tensor imaging (DTI), an imaging modality that collects data points from 51 directions, while HDFT is based on data from 257 directions. For the latter, the injury site was compared to the healthy side of his brain, as well as to HDFT brain scans from six healthy individuals.

Only the HDFT scan identified a lesion in a motor fiber pathway of the brain that correlated with the patient's symptoms of left-sided weakness, including mostly intact fibers in the region controlling his left leg and extensive breaks in the region controlling his left hand. The patient eventually recovered movement in his left leg and arm by six months after the accident, but still could not use his wrist and fingers effectively 10 months later.

Memory loss, language problems, personality changes and other brain changes occur with TBI, which the researchers are exploring with HDFT in other research protocols.

UPMC neurosurgeons also have used the technology to supplement conventional imaging, noted Robert Friedlander, M.D., professor and chair, Department of Neurological Surgery, Pitt School of Medicine, and UPMC Endowed Professor of Neurosurgery and Neurobiology. He is not a member of this research study.

"I have used HDFT scans to map my approach to removing certain tumors and vascular abnormalities that lie in areas of the brain that cannot be reached without going through normal tissue," he said. "It shows me where significant functional pathways are relative to the lesion, so that I can make better decisions about which fiber tracts must be avoided and what might be an acceptable sacrifice to maintain the patient's best quality of life after surgery."

Dr. Okonkwo noted that the patient and his family were relieved to learn that there was evidence of brain damage to explain his ongoing difficulties. The team continues to evaluate and validate HDFT's utility as a brain imaging tool, so it is not yet routinely available.

"We have been wowed by the detailed, meaningful images we can get with this technology," Dr. Okonkwo said. "HDFT has the potential to be a game-changer in the way we handle TBI and other brain disorders."

LSUSHC research identifies new experimental drug for stroke

2012-03-01T22:22:00.001-06:00

Too bad its patented.
http://www.lsusystem.edu/index.php/2012/03/01/lsushc-research-identifies-new-experimental-drug-for-stroke/
Research led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health Sciences Center New Orleans, has found that a synthetic molecule protected the brain in a model of experimental stroke. Dr. Bazan was issued a patent on the molecule called LAU-0901, a low molecular weight drug that crosses the blood-brain barrier. The findings are published in the March 2012 issue of Translational Stroke Research.

During an ischemic stroke, the most common kind, the body releases signals that cause neuroinflammation which leads to a buildup of chemicals that harm the brain. Platelet-activating factor (PAF) accumulates, and inhibition of this process plays a critical role in neuronal survival.

“LAU-0901 is able to reduce this incorrect signaling and inhibit the PAF receptor, which reduces multiple neuroinflammatory signals and greatly lessens the severity of damage in experimental stroke,” notes Dr. Bazan.

The research team used magnetic resonance imaging in conjunction with behavior and immunohistopathology to further study this novel therapeutic approach. The researchers report that LAU-0901, given two hours after the onset of experimental stroke, lessened the severity of brain damage, significantly reduced lesions in the brain, and improved coordination and movement. LAU-0901 produced no discernible side effects. These findings suggest LAU-0901 is a promising neuroprotectant that provides the basis for future therapeutics in patients suffering ischemic stroke.

Stroke is a leading cause of death and disability worldwide. Conventional therapies for ischemic stroke include thrombolytic therapy, prevention of inappropriate coagulation and thrombosis, and surgery to repair vascular abnormalities.Only one FDA-approved therapy exists for treatment of acute ischemic stroke, the thrombolytic tissue plasminogen activator (tPA), but only 5% of all ischemic stroke patients are eligible for treatment with tPA.

The research team also included Professor Ludmila Belayev and MD/PhD student Tiffany Niemoller Eady at LSU Health Sciences Center New Orleans, as well as Dr. Julio Alvarez Builla and other scientists from the University of Alcala, Spain, and Dr. Andre Obenaus at the University of Loma Linda.

New drug could protect brain from stroke damage

2012-03-01T15:16:00.005-06:00

Get going on more testing.
http://www.foxnews.com/health/2012/03/01/new-drug-could-protect-brain-from-stroke-damage/

A new drug appears to protect the brain against damage from stroke, even if administered hours after the stroke occurs, according to a new study in monkeys.

Monkeys given the drug had less dead brain tissue and showed more improvements on tests of brain function after a stroke, compared with monkeys that did not take the drug.

Testing on primates was important because, over the last half-century, there have been more than 1,000 drugs (So what are they?)aimed at preventing brain damage that have failed to work in people, even though they worked well in mice or rats, said study researcher Dr. Michael Tymianski, of the Toronto Western Hospital Research Institute in Canada.

The new findings show it is possible to protect a complex brain, similar to that of a human, against damage after stroke, Tymianski said.

In fact, Tymianski and colleagues have already tested the drug, which belongs to a group called PSD-95 inhibitors, in a small number of people. Their early studies suggest the drug is safe and effective in people as well, Tymianski said, and he hopes the drug will be available for people in three to four years.

Simulating strokes

The researchers induced strokes in cynomolgus macaques. Ten monkeys received the drug, delivered intravenously, while ten received a placebo. To increase their study's validity, the researchers stimulated strokes were likely larger than what would occur in people, Tymianski said.

The monkeys' brains were scanned using magnetic resonance imaging (MRI) one day and 30 days after their strokes, and the animals completed tests over the month to measure their brain function.

The drug reduced the amount of brain tissue at risk for damage by 55 percent after one day, and by 70 percent after one month, the researchers said.

Monkeys given the drug improved on the brain function tests over the study, while monkeys given the placebo did not.

Similar findings were seen even when the drug was administered three hours after stroke, Tymianski said.

Promising drug?

"It looks really promising," Dr. S. Thomas Carmichael, a neurologist at the University of California, Los Angeles, said of the findings. "They addressed a lot of past failings that have plagued this area of research," said Carmichael, who was not involved in the study.

PSD-95 inhibitors are thought to work by protecting brain cells from the destructive events that occur when cells are deprived of oxygen, as is the case with stroke. Several other research groups are also investigating their use as stroke treatments.

Some are concerned the drugs may be toxic in people because they inhibit the interactions of a brain protein required for normal brain function, said Dave Schubert, a professor and at the Salk Institute in La Jolla, Calif. And drug toxicity is usually revealed in late-stage clinical trials, because those patients receive the drug for much longer, Schubert said.

The study in monkeys was published Wednesday in the journal Nature. The researchers presented the findings from their studies in people this year at the International Stroke Conference.

Tymianski is president and CEO of NoNO Inc., a biotechnology company that makes NA-1, the drug used in the study.

Pass it on: Drugs known as PSD-95 inhibitors can protect monkey brains from damage after stroke, and the researchers hope the findings will be true in people too.

Trans Fats Linked to Stroke in Older Women

2012-03-01T14:39:00.002-06:00

Be careful out there. I hate these when they don't define older.
http://www.medpagetoday.com/Cardiology/Strokes/31434?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=03-01-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=

High trans fat intake may boost stroke risk for postmenopausal women, but aspirin appears to bring it back down, according to an observational study.

Women who ate the most trans fats were 39% more likely to have an ischemic stroke compared with those who had the least in their diet (P=0.048 for trend) Ka He, MD, ScD, MPH, of the University of North Carolina at Chapel Hill's School of Global Public Health, and colleagues found.

Aspirin use altered the link, though, with no effect of trans fat intake for women taking it (P=0.43 for trend) but a 66% elevated ischemic stroke risk for non-aspirin users with the highest trans fat consumption (P<0.01 for trend), they reported online in the Annals of Neurology.

"Our results highlight the importance of limiting the amount of dietary trans fat intake and using aspirin for primary ischemic stroke prevention among women, specifically postmenopausal women who have elevated risk of ischemic stroke," the group wrote.

Trans fats, which are typically found in processed food from partial hydrogenation of vegetable oils, are thought to raise heart disease risk by boosting cholesterol, inflammation, and endothelial dysfunction.

But the link between fats and stroke has been less straightforward, and two large studies of healthcare professionals found no association of trans fats with ischemic stroke.

Because those studies included relatively few strokes, He's group analyzed the more than 1,000 incident ischemic strokes in the prospective Women's Health Initiative Observational Study according to food frequency questionnaires filled out by the 87,025 generally healthy postmenopausal women who participated.

Total fat intake, cholesterol consumption, and other types of fats aside from trans fat showed no association with ischemic stroke.

For trans fat, the hazard ratios for ischemic stroke adjusted for age and ethnicity rose with trans fat intake compared with the lowest intake quintile that averaged 2.2 g per day (P=0.0002 for trend):

1.22 for the quintile that consumed an average 2.3 g per day (95% CI 0.99 to 1.51)
1.37 for the quintile that got an average 2.6 g per day (95% CI 1.11 to 1.68)
1.33 for the quintile that averaged 3.4 g per day (95% CI 1.09 to 1.64)
1.49 for the highest intake group who averaged 6.1 g per day (95% CI 1.22 to 1.82)

The association attenuated slightly but remained significant with further adjustment for factors such as fruit and vegetable and fiber in the diet, as well as socioeconomic factors, use of hormone replacement therapy, smoking and medical history, and use of medications including aspirin.

The impact of dietary trans fat was modified by aspirin use, which was consistent across all three types of trans fat isomers (P=0.04 to 0.002 for interaction), though not by use of statin medication or menopausal hormone therapy or alcohol intake.

"Increased platelet response to an agonist and inhibition after aspirin intake may at least in part explain the attenuated association between trans fat intake and ischemic stroke among aspirin users in this cohort," the researchers suggested.

Aspirin may make a difference in this population in particular because of the higher platelet reactivity among women and greater platelet aggregability with older age, they noted.

The group cautioned that they may have been underpowered to show an effect of statins in modifying the association with trans fat, but noted that fatty acid intake was a key measure in the food frequency questionnaires used.

Confounding was possible but unlikely, as the results remained consistent through several sensitivity analyses, they added.

GSK3 as a Sensor Determining Cell Fate in the Brain

2012-02-29T20:33:00.003-06:00

More stuff to research on hyperacute therapies.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275790/
Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics, and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favor a proliferative/survival state, while substrates positively regulated by GSK3 favor a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors) and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders.

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

2012-02-29T20:26:00.002-06:00

Something similar needs to be done for stroke.

http://scholar.google.com/scholar_url?hl=en&q=http://www.springerlink.com/index/NJUL186353100QW8.pdf&sa=X&scisig=AAGBfm34RZH6OQdFVEVqZN_qGKq9eVXxvQ&oi=scholaralrt

Abstract

Traumatic brain injury (TBI) initiates a complex cascade of secondary neurodegenerative mechanisms contributing to cell dysfunction and necrotic and apoptotic cell death. The injured brain responds by activating endogenous reparative processes to counter the neurodegeneration or remodel the brain to enhance functional recovery. A vast array of genetically altered mice provide a unique opportunity to target single genes or proteins to better understand their role in cell death and endogenous repair after TBI. Among the earliest targets for transgenic and knockout studies in TBI have been programmed cell death mediators, such as the Bcl-2 family of proteins, caspases, and caspase-independent pathways. In addition, the role of cell cycle regulatory elements in the posttraumatic cell death pathway has been explored in mouse models. As interest grows in neuroplasticity in TBI, the use of transgenic and knockout mice in studies focused on gliogenesis, neurogenesis, and the balance of growth-promoting and growth-inhibiting molecules has increased in recent years. With proper consideration of potential effects of constitutive gene alteration, traditional transgenic and knockout models can provide valuable insights into TBI pathobiology. Through increasing sophistication of conditional and cell-type specific genetic manipulations, TBI studies in genetically altered mice will be increasingly useful for identification and validation of novel therapeutic targets.

Mending the brain with a mechanical glove

2012-02-29T18:21:00.002-06:00

Just think, students came up with this.
http://www.northeastern.edu/news/stories/2012/02/capstonestrokerehab.html

Northeastern University student-researchers have created a post-stroke rehabilitation glove designed to increase hand strength through finger extension and improve cognitive ability to complete everyday tasks such as picking up a glass, turning a doorknob or unscrewing a soda bottle.

The innovative device, dubbed “Excelsior,” was designed for a senior capstone project under the direction of Constantinos Mavroidis, Distinguished Professor of Engineering, and Richard Ranky, a mechanical engineering doctoral candidate. The undergraduate team members included Aaron Bickel, Abhishek Singhal, Craig Pacella and Nisha Parekh, whose work was supported by a three-year, $270,000 grant from the National Science Foundation.

According to the Centers for Disease Control and Prevention, some 800,000 stroke cases occur in the United States each year. Ranky said survivors require physical therapy and ongoing exercise to regain mobility and dexterity. As he put it, “A major goal for patients post-stroke is regaining their fine motor control.”

Excelsior – which was developed using 3-D additive manufacturing with embedded sensors and can be customized to fit a patient’s hand – was designed with that goal in mind.

To improve cognitive function, users match colored LEDs (light-emitting diodes) on the device’s fingertips with those on external objects fashioned into household shapes, such as cups or doorknobs.

In preparation for designing the prototype, students interviewed physical therapists at Spaulding Rehabilitation Hospital in Boston who shed light on patient needs.

Pacella, a senior mechanical engineering major, praised his group’s final design. “No other device assists with opening the hand and has cognitive exercises like this,” he said. “Most commercial hand motion rehab devices don’t use sensors to measure range of motion and control of the fingers.”

Mavroidis, who has filed a provisional patent on the glove, plans to license and commercialize the rehab device, which would cost patients approximately $200. But there’s work to be done. “It still needs to become more user-friendly, stronger and thinner,” Mavroidis explained.

Pacella said programming and developing circuit boards for the prototype forced him outside of his comfort zone, which, he said, would serve him well in his first professional job.

“There’s no such thing as a job in only mechanical engineering,” Pacella said. “In the real world, you need to understand other disciplines, which you can only learn through experience.”

Ranky agreed, highlighting the value of experiential learning. “Working on a capstone project is different from solving a problem in class where there is only one solution,” he said. “Capstone is as close as you can get to the real world.”

Technology To Prevent Stroke Demonstrated In JoVE

2012-02-29T18:16:00.002-06:00

Practically anything would be better than rat poison.
http://www.medicalnewstoday.com/releases/242277.php
In the United States alone, approximately 6 million people suffer from an irregular heartbeat called atrial fibrillation (AF), and since the incidence increases with age, it is predicted that 15.9 million Americans will be affected by 2050. The most devastating side effect of AF is stroke, but a new device from Boston Scientific may prevent them from occurring.

Researchers from Atritech, now part of Boston Scientific, developed the WATCHMAN device, a small mesh umbrella that can be inserted into part of the heart cavity to prevent the formation of blood clots that cause strokes.

Currently, the anti-coagulant drug warfarin is used to prevent strokes, but the drug comes with other risks.

"Warfarin has a lot of side-effects. One major side-effect is the bleeding risk," said paper author Dr. Sven Mobius-Winkler. "Therefore, only 50 percent of the patients who should take Warfarin actually take it."

The WATCHMAN device gives patients another option. It has already been approved for use in the European Union and Australia, and secured investigational approval from the FDA in 2009.

To help train doctors how to use the device, doctors from the University of Leipzig Heart Center in Germany are publishing the full WATCHMAN placement procedure in the Journal of Visualized Experiments (JoVE), the world's first and only peer-reviewed, PubMed indexed, science and medicine video journal.

"Intervention and closure of the left atrial appendage is a complex procedure," said Dr. Mobius- Winkler. "For inexperienced physicians, it is hard to learn this procedure and therefore the video can help by doing step-by-step the implantation."

"The WATCHMAN device will give patients with atrial fibrillation another option rather than anti-coagulant drugs," said JoVE Editor Dr. Robert Dolan. "This article demonstrates the implantation of the device and will help clinicians gain expertise with the procedure, helping many of the patients who are unable or unwilling to take warfarin."

Study: Old flu drug speeds brain injury recovery

2012-02-29T17:41:00.002-06:00

Lets start studying this for stroke.
http://www.lasvegassun.com/news/2012/feb/29/us-med-brain-injury-drug/

Researchers are reporting the first treatment to speed recovery from severe brain injuries caused by falls and car crashes: a cheap flu medicine whose side benefits were discovered by accident decades ago.

Severely injured patients who were given amantadine got better faster than those who received a dummy medicine. After four weeks, more people in the flu drug group could give reliable yes-and-no answers, follow commands or use a spoon or hairbrush _ things that few of them could do at the start. Far fewer patients who got amantadine remained in a vegetative state, 17 percent versus 32 percent.

"This drug moved the needle in terms of speeding patient recovery, and that's not been shown before," said neuropsychologist Joseph Giacino of Boston's Spaulding Rehabilitation Hospital, co-leader of the study. He added: "It really does provide hope for a population that is viewed in many places as hopeless."

Many doctors began using amantadine for brain injuries years ago, but until now there's never been a big study to show that it works. The results of the federally funded study appear in Thursday's New England Journal of Medicine.

A neurologist who wasn't involved in the research called it an important step. But many questions remain, including whether people less severely injured would benefit, and whether amantadine actually improves patients' long-term outcome or just speeds up their recovery.

Each year, an estimated 1.7 million Americans suffer a traumatic brain injury. Falls, car crashes, colliding with or getting hit by an object, and assaults are the leading causes. About three-quarters are concussions or other mild forms that heal over time. But about 52,000 people with brain injuries die each year and 275,000 are hospitalized, many with persistent, debilitating injuries, according to government figures.

With no proven remedies to rely on, doctors have used a variety of medicines approved for other ailments in the hopes that they would help brain injury patients. Those decisions are based on "hunches and logic rather than data," said Dr. John Whyte, of the Moss Rehabilitation Research Institute in suburban Philadelphia. He led the study along with Giacino.

Amantadine (uh-MAN'-tah-deen), an inexpensive generic, was approved for the flu in the mid-1960s. The first inkling that it might have other uses came a few years later when it appeared to improve Parkinson's symptoms in nursing home patients who got it. It was found to have an effect on the brain's dopamine system, whose many functions include movement and alertness, and it was later approved for Parkinson's.

It's now commonly used for brain injuries, and the researchers felt it was important to find out "whether we're treating patients with a useful drug, a harmful drug or a useless drug," Whyte said.

The study was done in the U.S., Denmark and Germany and involved 184 severely disabled patients, about 36 years old on average. About a third were in a vegetative state, meaning unconscious but with periods of wakefulness. The rest were minimally conscious, showing some signs of awareness. They were treated one to four months after getting injured, a period when a lot of patients get better on their own, Giacino noted.

They were randomly assigned to receive amantadine or a dummy drug daily for four weeks. Both groups made small but significant improvement, but the rate of recovery was faster in the group getting amantadine. When treatment stopped, recovery in the drug group slowed. Two weeks later, the level of recovery in the two groups was about the same.

There was no group difference in side effects, which included seizure, insomnia and rigid muscles.

The study was short, and the effect on long-term outcome is unknown. But Giacino said the drug still has value even if it only hastens recovery.

"What condition would we not jump for joy if we could have it over with faster?" he said.

The study didn't include those with penetrating head injuries, like the gunshot wound former Rep. Gabrielle Giffords suffered, but Giacino said the drug should have similar effects in those patients. Whether it would work in patients with brain injuries not caused by trauma, such as a stroke, isn't known.

Whyte said the researchers want to test the drug for longer periods.

Dr. Ramon Diaz-Arrastia said the results were welcome news in a field that has seen many failed efforts. He is director of clinical research at the government's Center for Neuroscience and Regenerative Medicine, which works with the military and government scientists on brain injury research.

"It's an important step toward developing better therapies," he said.

Since amantadine is so commonly used, he said U.S. troops with severe brain injuries in Iraq or Afghanistan probably get it, or should get it now. Since 2000, some 233,000 troops have suffered traumatic brain injuries, including about 6,100 serious cases, many of them from bomb blasts or shrapnel.

Laura Bacon said amantadine seems to be helping her brother recover from a car accident in Vermont last October. Nicholas Gnazzo, 47, of Rochester, N.H., was in a coma for weeks before he was taken for rehabilitation to Spaulding, where doctors put him on amantadine in January.

Since then he has been more alert, able to communicate with nods or gestures _ like pointing to his eyes when he wants his glasses, his sister said. Giacino agreed her brother has gotten better, but whether it is because of the drug can't be determined. Gnazzo wasn't part of the study.

"It's been four months now, and we know we still have a long way to go," Bacon said. "Anything that could be faster _ or feel faster to us _ is a positive."

Antibodies in Spinal Fluid Post-Stroke Puzzling

2012-02-29T13:03:00.003-06:00

I think these researchers are looking at this wrong, they are assuming that these antibodies are the cause of the stroke rather than a result.
http://www.medpagetoday.com/Cardiology/Strokes/31410?utm_source=cardiodaily&utm_medium=email&utm_content=aha&utm_campaign=02-29-12&eun=gd3r&userid=424561&email=oc1dean@yahoo.com&mu_id=

Patients with acute stroke were more likely than those with other conditions to have antibodies in their cerebrospinal fluid, researchers found.

Of patients who received a lumbar puncture, nearly a quarter (24.8%) of those with acute stroke had intrathecal antibodies, compared with just 2.5% of patients with other conditions (P<0.001), according to Harald Prüss, MD, of the Charité University of Medicine Berlin, and colleagues.

"The strong association between cerebrospinal fluid-specific immunoglobulin synthesis and stroke suggests a role in the development of cerebral ischemia and might constitute an immunologically defined stroke subgroup," the researchers wrote online in Archives of Neurology.

The finding "demands a systematic prospective analysis of cerebrospinal fluid and serum samples to determine the time kinetics and pathogenicity of antibodies," they wrote.

Immune mechanisms have been considered to explain some ischemic strokes, but the role of intrathecal antibodies remains unclear because diagnostic tests are not routinely performed on cerebrospinal fluid in patients after cerebral ischemia.

In the current study, Prüss and colleagues examined data from 3,050 consecutive patients with ischemic stroke who were hospitalized at their center from 2005 to 2009.

Only 318 (10.4%) underwent a lumbar puncture within 96 hours after symptom onset. Indications included seizures, suspected central nervous system infection or vasculitis, pronounced agitation or disorientation, suspected leptomeningeal carcinomatosis, mitochondriopathy, vasculopathy, or diagnostic uncertainty.

The researchers matched those 318 patients with 79 control patients who did not have a stroke but received a lumbar puncture during a diagnostic workup for headache, diabetic oculomotor or abducens nerve palsy, idiopathic facial nerve palsy, or dizziness.

The patients with stroke were more likely to have cerebrospinal fluid-specific immunoglobulin synthesis than the controls, as measured by the presence of oligoclonal immunoglobulin bands.

The high, nearly 25% prevalence of antibodies in the cerebrospinal fluid of patients with stroke "may point to a direct association between cerebrospinal fluid-specific immunoglobulin synthesis and focal cerebral ischemia," the authors wrote.

Among the patients with stroke, one-third had blood-brain barrier dysfunction and 18.1% had pleocytosis, with no differences in the rates based on the presence or absence of the antibodies.

There were also no differences in the frequency of oligoclonal bands, pleocytosis, increased protein in the fluid, age, and sex based on whether the patients had had a prior stroke.

Of the patients with stroke who did not have intrathecal antibodies after the first lumbar puncture, 12 underwent a second puncture. Half had antibodies after the second puncture, which suggests that "the percentage of patients with oligoclonal band-positive stroke might increase further with longer follow-up," according to Prüss and colleagues.

They noted that stroke-associated intrathecal immunoglobulin synthesis could result from one of three options:

Unidentified inflammatory disease
Undetected previous ischemic degeneration of neuronal tissue with repeated presentation of central nervous system antigen to the immune system
Polyclonal nonspecific B-cell activation secondary to brain damage

"The second explanation might be relevant to the high proportion of patients with oligoclonal bands already present at the time of their first clinically detected stroke," the authors wrote. "The finding of oligoclonal bands in patients with transient ischemic attacks supports this notion and implies relevance for predisease stages."

A Novel Mechanism For Protecting The Adult Brain In Times Of Oxygen Deprivation Inspired By Naked Mole-Rats

2012-02-28T15:27:00.003-06:00

Another option for stopping the cascade of neuronal death. Who is going to push researchers to find out more and create a therapeutic approach to this?
http://www.medicalnewstoday.com/releases/242172.php
Could blind, buck-toothed, finger-sized naked mole-rats harbor in their brain cells a survival secret that might lead to better heart attack or stroke treatments?

University of Illinois at Chicago biologist Thomas Park and colleagues at UIC and the University of Texas Heath Science Center at San Antonio think the subterranean lifestyle of the pasty-looking rodents may indeed hold clues to keeping brain cells alive and functioning when oxygen is scarce. The key may lie in how brain cells regulate their intake of calcium.

"Normally, calcium in brain cells does wonderful things, including forming memories," says Park, who is professor of biological sciences at UIC. "But too much calcium makes things go haywire."

Brain cells starved of oxygen can't regulate calcium entry, and too much calcium in the cell is lethal. When a heart attack or stroke prevents oxygenated blood from reaching the brain, brain damage or death results.

Naked mole-rats, however, are very tolerant to oxygen deprivation, or hypoxia -- as are human newborns, whose brain cells have calcium channels that close during oxygen deprivation, protecting the cells from calcium overdose. With age, these calcium channels no longer close, which normally isn't a problem -- except during a heart attack.

Naked mole-rats retain a tolerance for oxygen deprivation into adulthood. Park and his colleagues measured calcium entry in brain tissue that had been kept under oxygen-poor conditions, reporting their findings online Feb. 21 in PLoS One.

"We knew the adults of this unusual mammal had brains that, like infant humans, were very tolerant to oxygen deprivation," he said. "We wanted to know if the adult naked mole-rats used the same strategy as babies to prevent calcium entry. This is exactly what we found."

Park thinks this strategy is an evolutionary adaptation by mole-rats, which live in the hundreds underground in tight, oxygen-deprived conditions.

"Imagine 200 mice living in a shoe box buried four feet under the ground -- things are going to get bad fast," he said.

The researchers think they have identified a novel mechanism for protecting the adult brain in times of oxygen deprivation.

"Developing this target into a clinical application is our next goal," he said. "We need to find a way to rapidly up-regulate the infant-type of calcium channels. Adult humans actually have some of these channels already, but far fewer than infants."

Park, who for years has studied naked mole-rats and their unusual adaptations, thinks the latest findings "are just the tip of the iceberg" of what we can learn from the rodents. Their homes are not only oxygen-poor, but rich in carbon dioxide and ammonia -- conditions that would make most animals ill. Yet mole-rats have evolved to suppress pain and even cancer.

"The more we study these creatures," said Park, "the more we learn."

Ephrin-A1-Mediated Dopaminergic Neurogenesis and Angiogenesis in a Rat Model of Parkinson's Disease

2012-02-26T21:32:00.003-06:00

I know this is for Parkinsons but it does have some interesting possibilities in migration and signalling.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0032019

Abstract Top

Cells of the neural stem cell lineage in the adult subventricular zone (SVZ) respond to brain insult by increasing their numbers and migrating through the rostral migratory stream. However, in most areas of the brain other than the SVZ and the subgranular zone of the dentate gyrus, such a regenerative response is extremely weak. Even these two neurogenic regions do not show extensive regenerative responses to repair tissue damage, suggesting the presence of an intrinsic inhibitory microenvironment (niche) for stem cells. In the present study, we assessed the effects of injection of clustered ephrin-A1-Fc into the lateral ventricle of rats with unilateral nigrostriatal dopamine depletion. Ephrin-A1-Fc clustered by anti-IgG(Fc) antibody was injected stereotaxically into the ipsilateral lateral ventricle of rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine, and histologic analysis and behavioral tests were performed. Clustered ephrin-A1-Fc transformed the subventricular niche, increasing bromodeoxyuridine-positive cells in the subventricular area, and the cells then migrated to the striatum and differentiated to dopaminergic neurons and astrocytes. In addition, clustered ephrin-A1-Fc enhanced angiogenesis in the striatum on the injected side. Along with histologic improvements, behavioral derangement improved dramatically. These findings indicate that the subventricular niche possesses a mechanism for regulating both stem cell and angiogenic responses via an EphA–mediated signal. We conclude that activation of EphA receptor–mediated signaling by clustered ephrin-A1-Fc from within the lateral ventricle could potentially be utilized in the treatment of neurodegenerative diseases such as Parkinson's disease.

Roles of 5HT1A receptor in CNS neurogenesis and ADAM21 in spinal cord injury

2012-02-26T21:25:00.001-06:00

Even if this is for spinal cord injury we need the knowledge gained by this.
http://gradworks.umi.com/34/89/3489325.html

Abstract:

These studies set out to identify strategies to rescue and repair the adult nervous system. First, we investigated the role of ciliary neurotrophic factor (CNTF) in 5HT1A receptor-induced neurogenesis in the rodent brain. Systemic treatment with an agonist, 8-OH-DPAT, increased neurogenesis only in rats and not mice, and only in one of the two neurogenic regions. This increase was not mediated by CNTF. These data suggest that translation of 5HT1A-based studies to human cell replacement therapies should be reconsidered. Secondly, the role of the plasticity-associated metalloprotease ADAM21 after spinal cord injury was investigated by comparing ADAM21-deficient mice to their wildtype littermates. No differences in behavioral or histology were found. However, a comprehensive metalloproteinase gene array revealed that ADAM21 regulates a cluster of inflammatory genes following injury. This leaves a potential for discovery of specific pharmaceutical ADAM21 inhibitors to reduce detrimental inflammatory processes following spinal cord injury.

full dissertation here:

Billiards stroke rehab

2012-02-26T19:50:00.004-06:00

I was in northern Minnesota this weekend visiting a friend who owns a bowling alley. My bowling was not good the balls that fit my fingers were 14-16 lbs and at that weight I can't really control the swing very well, my regular bowling is with a 10 lb. ball. But the really fun part was playing bottle billiards. The official rules are listed here. Our rules are slightly different, you can't start scoring until you Carom the cue ball off both object balls, either object ball sank in a pocket is 1 point, a carom during a game is 2 points. We use an empty plastic soda bottle. This requires you to really stretch your arm out straight, loosen your fingers or thumb to guide the cue stick. My modification is to place the cue in crook of my wrist or sometimes underneath my wrist. I tried once to put the cue between my fingers but that only resulted in not being able to move the cue at all due to finger spasticity. We played 4 games and a lot of fun was had by all, especially the last game where my team won 31-0. The bars up there had dart games also so that would probably be another therapeutic possibility. So join your friends at the bars and play pool or darts with them. Ordering a diet Coke is acceptable.

Stroke Rehabilitation with PEMF Therapy

2012-02-24T09:20:00.003-06:00

I'm really skeptical on this one, they talk about regular therapy at the same time so it is impossible to determine which one actually works.
http://www.drpawluk.com/stroke-rehabilitation-with-pemf-therapy/

In a just published study (Kakuda), high-intensity, low-frequency pulsed electromagnetic fields were used in patients’ stroke rehabilitation. The patients had their strokes within one year to nine a half years before treatment with the PEMFs. During a 15 day elective hospitalization set up specifically for this program, each patient received 22 treatment sessions of 20-min low-frequency PEMF and 120-min intensive OT daily. The PEMF of 1 Hz was applied to the side of the head opposite the area of the stroke, i.e. on the same side as the paralysis. The intensive OT, consisting of 60-min one-to-one training and 60-min self-exercise, was provided after the application of low-frequency PEMF, using standardized protocols and objective measures for the impact of treatment. Improvements were persistently seen up to 4 weeks after discharge in 79 of the 204 studied patients. Longer-term assessments were not conducted. Statistical analysis found no significant relationship between baseline parameters and indexes of improvement in motor function. The authors concluded that the 15-day inpatient PEMF treatment plus OT protocol is a safe, feasible, and clinically useful neurorehabilitative intervention for post-stroke patients with upper limb paralysis. The response to the treatment was not influenced by age or time after stroke onset. The major drawback of this study was that there was no comparison group using sham PEMF treatment.

PEMFs are expected to influence nerve cell firing/function of selected brain areas. It appears to be that low-frequency ≤ 1 Hz suppresses while high-frequency ≥ 5 Hz activates local neural activities. There was the question of which side of the brain to stimulate, the side with the lesion or the opposite side. Several randomized controlled trials have confirmed that low-frequency PEMF applied to the brain hemisphere opposite to the side of damage (non-lesional) can significantly improve motor function of the affected upper limb in post-stroke patients. It is speculated that exposure to the non-lesional hemisphere reduces possibly protective nerve function inhibition by the non-lesional hemisphere towards the lesional hemisphere, leading to facilitation of beneficial functional reorganization in the lesional hemisphere. Intensive occupational therapy (OT), especially using constraint-induced movement therapy (CIMT) for upper limb hemiparesis also appears to activate areas around the stroke lesion in chronic stroke patients. In chronic stroke, CIMT is currently considered to be most useful. In another study using high-frequency PEMF with CIMT over the lesional hemisphere daily for two weeks, compared to patients treated with CIMT only, improvement of motor function was not significantly different.

To be in the study the patients had to meet the following criteria: 1) ability, at least subjectively, to flex all the fingers of the affected upper limb in full range of motion. 2) Age between 18-90 years. 3) Time after the stroke more than 12 months. 4) Only a single-sided stroke. 5) No cognitive impairment with a pretreatment Mini Mental State Examination score of more than 26. 6) Being in a plateau state for at least 3 months. 7) No history of seizure within preceding year. 9) No documented epileptic discharge on pretreatment electroencephalogram. 10) No current use of antiepileptic medications for the prevention of seizure. 11) No pathological conditions known to be contraindications for PEMF.

In the current study, follow-up evaluation after discharge showed persistent improvement of motor function of the affected upper limb up to four weeks after treatment ended. The duration of improvement of motor function of the affected upper limb appears to be relatively short after a single session of low-frequency PEMF. A different study reported that the improvement induced by application of low-frequency PEMF to the non-lesional hemisphere daily for five consecutive days was maintained for two weeks after intervention. In yet another study, the improvement of motor function of the affected upper limb in patients who received CIMT was also maintained up to several months after the intervention. Whether there are longer-term effects using each of the two interventions remains unknown for now. What is also not known is whether continued use of PEMFs in the home setting long-term may continue to show improvements. This may be expected to be true given that the brain tends to repair very slowly, even given appropriate stimuli.

This study also showed no significant relationship between any of the six tested baseline parameters and the response to the intervention. The intervention can produce beneficial functional reorganization even in elderly patients and in those whose strokes were years earlier. Since this study did not include acute/subacute stroke patients within one year after onset, it remains unknown if earlier application of the protocol during the acute/subacute phase of stroke can produce more functional improvement than those seen in our patients. It has been reported that beneficial functional reorganization is higher in acute/subacute phase than in later phases of stroke.

While more research clearly needs to be done, this study is encouraging in showing that the combination of higher intensity PEMF and occupational therapy improves function, even in patients who had their strokes over a year earlier, and in some cases up to nine years earlier. Additionally, this study was performed in a hospital setting for a limited period of time using very expensive rTMS PEMF, with limited availability equipment. While not proven, it may not be unreasonable to expect that a home-based, high intensity PEMF system may produce similar results. A combination of low and high frequencies may be even better, some reducing nerve cell firing, as would be desirable with spasticity, and others increasing nerve cell firing, where there is a reduction in neuron function. It is generally axiomatic in medicine that little gain in function is likely to happen in these patients after the first 3 to 6 months following a stroke, with conventional PT/OT alone. So any therapeutic approach that is not likely be toxic or invasive, such as higher intensity PEMF , has a good chance of being able to provide benefit, and may well be worth considering.

Another just recently published study (Avenanti) of higher intensity, low frequency PEMF for stroke, investigated the long-term behavioral and neurophysiologic effects of combined higher intensity PEMF and physical therapy (PT) in chronic stroke patients with mild motor disabilities more than 6 months poststroke. In this study, thirty patients were enrolled in a double-blind, randomized, single-center clinical trial. They each received 10 daily sessions of 1 Hz higher intensity PEMF over the intact, that is nonaffected, motor cortex, with either real (R) or sham (S) approaches, administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition, and corticospinal excitability and they were assessed for 3 months after the end of treatment. The researchers found that treatment induced progressive rebalancing of excitability in the 2 brain hemispheres and a reduction of inter-hemispheric inhibition in the R groups. PT produced improvements in all groups. The aspects of functions that were trained showed only small and transitory improvements in the S patients. The R group had greater behavioral and neurophysiologic improvements especially in the group receiving R treatment before PT (R-PT), with robust and stable improvements. The post PT-R group showed a slight decline in their improvement over time. They concluded that priming PT with inhibitory higher intensity PEMF before the PT (in the hemisphere opposite to the stroke lesion) is optimal to boost brain plasticity related to the functions trained with PT and rebalance motor excitability and suggests that higher intensity PEMF is a valid and promising approach for chronic stroke patients with mild motor impairment.

These patients were enrolled as outpatients in a Neurorehabilitation clinic. They were included if they had a unilateral stroke, greater than six months after the first ever stroke, and had mild upper limb motor deficit. Anyone with a seizure disorder was excluded. The higher intensity PEMF was applied immediately before or after PT. There were eight patients in each experimental group with a total of 14 patients in the sham treatment arm. Treatment lasted for 10 days with two PEMF sessions per day, of 25 min. each, and 45 min. of standard task oriented upper limb exercises. The PEMF was applied to the motor cortex. The sham was the same activated coil applied perpendicularly to the scalp so that no current was induced in the brain. To check stability, two pretreatment evaluations were performed two weeks and one day before starting treatment. Post treatment evaluations were performed at 1, 7, 14, 30, and 90 days post treatment. Neural excitability of both hemispheres was assessed at baseline, pretreatment, day six [pre treatment] and at each of the post treatment follow-ups.

The exciting aspect of this study was that they actually checked for cortical excitability. Chronic stroke patients typically show less excitability on the affected side of the brain compared to the opposite side of the brain. In a normal non-stroke brain there is a cross communication between the sides of the brain where each side balances the other with inhibition and stimulation. Because of the damage to the side affected by the stroke the opposite side becomes uninhibited and can irritate the affected side, creating spasticity in the affected extremity. Before the study, the researchers believed that doing higher intensity PEMF before PT could potentially prime functional neural networks for the PT intervention to work better, leading to superior outcomes. This study provided evidence that higher intensity PEMF stimulation induces reduction of interhemispheric inhibition from the intact side of the brain to the affected side, long-term potentiation of excitability of the affected side leading to improved and obvious functional improvements, in particular when PT is preceded by the higher intensity PEMF. One to three months after treatment the group receiving PT first started to show a decline in performance and excitability of the affected side. In the group receiving higher intensity PEMF first, the outcomes remained stable over time by boosting brain plasticity caused by use of the brain and the affected extremity, mainly by stabilizing the physical learning processes of the brain. They found evidence of a daily, cumulative lowering of excitability in the intact hemisphere. This was paralleled by a strong cumulative increase in the excitability of the affected hemisphere. This study provides direct neurophysiologic evidence that 10 days is more effective than five days of higher intensity PEMF treatment. The sham PEMF stimulation group showed only a modest improvement lasting only a few weeks with no significant changes in excitability. This is not surprising since the PT was relatively short, patients were all chronic poststroke, and all had already received cycles of rehabilitation before. Even though it is known that PT this late after stroke is less effective, this study indicates that brain stimulation may overcome this limitation.

The practical importance of this randomized controlled trial, is that, even post stroke, at least up to six months afterward the stroke, the use of higher intensity PEMFs and PT may produce significant improvements in function, that was thought to be lost permanently. The questions that ultimately remain is whether similar benefits can be seen more than six months after the stroke and whether various higher intensity PEMF systems may produce similar results. Given the lack of toxicity for PEMF therapies, below the level of inducing seizures or contractions, post stroke patients may find significant benefit from these therapies.

Higher intensity PEMF therapy systems that could be considered for stroke management, in the light of the studies above, would include the PEMF 100, Curatron XP/PC, Sota and Almag. The PEMF 100 and Curatron would be expected to provide the better results, because of their frequencies and intensities.

The mystery of the missing brain cells

2012-02-23T15:40:00.002-06:00

Does neurogenesis exist in humans? Register at the site to read it all.
http://www.newscientist.com/article/mg21328521.600-the-mystery-of-the-missing-brain-cells.html

The idea that we can grow new neurons has brought tantalising hope of repairing the brain after injury and disease. But could it be based on wishful thinking?

I AM sitting at a lab bench peering down the microscope at the brain of a chicken embryo. Dense networks of delicate young nerve fibres surround patches of newborn cells with their DNA stained dark brown.

I am witnessing the end products of neurogenesis, the birth of new brain cells. It is one of the hottest topics in neuroscience, and the idea that we can boost the growth of new brain cells with various kinds of physical or mental exercise seems to have equally taken hold of the public imagination. On top of this is the exciting prospect that we could one day use new neurons to repair the brain after injury or disease.

But does it really happen? While there is good evidence that adult neurogenesis takes place in animals, there is reason to believe that does not necessarily apply to our own species. "Everyone wants to believe that functional neurogenesis happens in adult humans, everyone wants to believe that we can repair damaged brains," says Andrew Lumsden, head of the MRC Centre for Developmental Neurobiology at King's College London, where I saw the chicken brain. "But there's precious little evidence for it."

The current faith in our brains' regenerative abilities is in fact something of a reversal. For most of the last century, it was thought that neurogenesis was restricted to our time in the womb. "Once development was ended the founts of growth dried up irrevocably," wrote Santiago Ramón y Cajal, the 19th-century Spanish anatomist seen as the founder of modern neuroscience. "In the adult, the nerve paths are immutable."

One basis of this belief was our limited capacity to recover after a stroke or a blow to the head. Such injuries can have long-lasting effects on abilities like speech and movement. Plus the brain is so much more complex than organs with proven regenerative powers, such as the skin and liver. "How would new neurons usefully integrate into complex neural networks after the connectional plan of the brain is complete?" asks Lumsden. "One side effect of having a large and complex brain is that you wouldn't want naive newcomers barging in."

What Makes Good Cholesterol Go Bad?

2012-02-23T14:51:00.001-06:00

And maybe they will eventually find out why cholesterol turns into plaque.
http://www.everydayhealth.com/high-cholesterol/0223/what-makes-good-cholesterol-go-bad.aspx

Researchers have discovered how specific proteins in the blood transform HDL cholesterol (the good kind) into LDL Cholesterol (the bad kind). Here's how it works, plus ways to amp up your good cholesterol levels through diet and exercise.

Blame it on a tiny, banana-shaped protein molecule called CETP, which stands for cholesteryl ester transfer protein.

Research from the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) has revealed how CETP turns good cholesterol (high density lipoproteins, or HDL) into bad cholesterol (low density lipoproteins, LDL).

Lipoproteins are substances that carry cholesterol throughout the body. LDLs do so in a way that can clog arteries — blocking blood flow, and potentially causing heart disease or stroke. Hence the “bad” label. HDLs, on the other hand, carry cholesterol out of the bloodstream and into the liver, where it’s excreted. That way, it doesn’t build up in the arteries.

It turns out that CETP molecules transfer cholesterol from those good HDLs to bad LDLs via a tunnel that runs through its center.

The findings, published in the journal Nature Chemical Biology, could lead to more efficient ways of preventing the development of heart disease. “Our model identifies new interfaces of CETP that interact with HDL and LDL and delineates the mechanism by which the transfer of cholesterol takes place,” says Gang Ren, PhD, of Berkeley Lab’s Molecular Foundry, who led the study. “This is an important step toward the rational design of next generation CETP inhibitors for treating cardiovascular disease.”

Athersys, University Hospitals partner for clinical trials of MultiStem for stroke

2012-02-23T12:25:00.004-06:00

Earlier I posted about using this for TBI. I can't tell if this is for chronic or acute. I do wonder how they plan to get thru the blood-brain barrier. Everyone should clamor to get involved.
http://www.medcitynews.com/2011/09/athersys-reveals-plans-for-phase-2-stroke-clinical-trial/
Stem cell developer Athersys (NASDAQ:ATHX) has taken the next of many steps toward commercializing its MultiStem therapy for stroke, the most promising application for the therapy.

The Cleveland-based company detailed its plans for a phase 2 ischemic stroke clinical trial that’s estimated to involve about 140 patients, according to ClinicalTrials.gov, a website maintained by the National Institutes of Health.

The double-blind, randomized, placebo-controlled study is designed to evaluate the safety and effectiveness of treating stroke patients with MultiStem, an off-the-shelf stem cell treatment derived from the bone marrow of adults or other nonembryonic sources.

The trial is scheduled to start enrollment this month, with October 2013 estimated as the time frame for final data collection. The trial is expected to be completed by November 2014.

A company official declined comment.

The company believes MultiStem could represent a significant advancement in treating ischemic stroke patients. The technology has shown promise in reducing inflammation, protecting damaged tissue and forming new blood vessels.

Ischemic stroke is caused by a blood clot in the brain and accounts for 87 percent of all stroke cases.

As for the reason that stroke is the most promising application of MultiStem — which is also being investigated for the treatment of heart attack, inflammatory bowel disease, orthopedics and blood diseases — it’s simple: stroke represents the largest market.

CEO Gil Van Bokkelen has pegged the potential stroke market at $15 billion.

Still, the company faces a long, bumpy road to commercialization, with any application of MultiStem unlikely to hit the market for at least four or five years.

Chantix Shows Promise for Ataxia

2012-02-23T12:17:00.002-06:00

And since stroke can cause ataxia research is needed to see if it would help stroke survivors.
http://www.dddmag.com/news-Chantix-Shows-Promise-for-Ataxia-22312.aspx

A nicotinic drug approved for smoking cessation significantly improved the walking ability of patients suffering from an inherited form of ataxia, reports a new clinical study led by University of South Florida researchers.

The randomized controlled clinical trial investigated the effectiveness of varenicline (Chantix) in treating spinocerebellar ataxia type 3, or SCA3. The findings were published online earlier this month in Neurology, the journal of the American Academy of Neuroscience.

Lead author Dr. Theresa Zesiewicz and colleagues at the USF Ataxia Research Center collaborated with researchers from Beth Israel Deaconess Medical Center in Boston, MA, and from the David Geffen School of Medicine at UCLA in Los Angeles, CA.

Spinocerebellar ataxia impairs the brain and spinal cord causing progressive difficulty with coordination of movements, including walking. The uncoordinated movements, or ataxia, is a neurological symptom with no treatment or cure and can lead to serious fall-related injuries.

"This is the first clinical trial in patients with ataxia showing that nicotinic acetycholine agonists improve symptoms associated with the ability to stand straight and walk," said Dr. Zesiewicz, professor of neurology and director of the USF Ataxia Research Center. "Patients receiving varenicline could walk with more ease, with less help and faster than those in the placebo group."

The double-blind multicenter study evaluated 20 adult patients with genetically confirmed SCA3. Half the patients received 1 mg. of varenicline twice a day, and the other half received placebo. At the end of the eight-week study, patients taking varenecline performed significantly better on measures of gait, stance, rapid alternating movements and a timed 25-foot walk than those who did not. The drug was fairly well tolerated, with mild nausea being the most common side effect.

The study authors suggest that varenicline's ability to improve ataxia may be associated with the drug's ability to act at several different sites in the brain affected by nicotine.

Study co-author Lynn Wecker, PhD, a distinguished research professor at USF Health, is investigating the cellular and molecular mechanisms mediating the effects of varenicline and other nicotinic agonists. Dr. Wecker and colleagues, supported by a five-year grant funded by the National Institute of Neurological Disorders and Stroke, have shown that several drugs affecting neuronal nicotinic receptors improve gait and balance in an animal model of SCA3.

Further preclinical research is needed to understand how nicotinic acetylcholine agonists improve ataxia, and larger clinical studies with more patients are needed to identify other neurodegenerative diseases that may benefit from nicotinic medications, the authors conclude.

Invade and conquer: Nicotine's role in promoting heart and blood vessel disease

2012-02-23T12:02:00.003-06:00

The bad side of nicotine, you'll have to consult your doctor for the benefits during rehabilitation.
http://www.eurekalert.org/pub_releases/2012-02/aiop-iac022312.php
Cigarette smoke has long been considered the main risk factor for heart disease. But new research from Brown University in Providence, R.I., shows that nicotine itself, a component of cigarette smoke, can contribute to the disease process by changing cell structure in a way that promotes migration and invasion of the smooth muscle cells that line blood vessels. In particular, invading cells can remodel structures called podosomes, and this leads to further degradation of vessel integrity.

Ultimately, this cellular migration and invasion process gives rise to the formation of vessel-clogging fatty deposits known as plaque – the hallmark of heart and blood vessel disease. The results on the nicotine-podosome link will be presented at the 56th Annual Meeting of the Biophysical Society (BPS), held Feb. 25-29 in San Diego, Calif.

If confirmed in further studies, the finding that nicotine itself promotes vessel damage by changing podosomes appears to question the health benefits of helping people quit smoking through smokeless nicotine delivery agents such as gum or patches.

"The finding that nicotine is as effective as cigarette smoke in enhancing cellular structural changes, and breakdown of scaffold proteins by vascular smooth muscle cells, suggests that replacing cigarette smoking by nicotine treatment may have limited beneficial effects on atherosclerosis," notes lead researcher Chi-Ming Hai, professor of medical science in the department of molecular pharmacology, physiology, and biotechnology at Brown University.

Hai's research illuminates the multistep process of plaque formation, and suggests that a new powerful player, nicotine, may be involved. The plaque formation process begins as a response to cellular injury, and progresses to destructive and chronic inflammation of the vessel walls that attracts mobs of white blood cells, further inflaming the vessels. This damage-causing inflammation can be triggered by chemical insults from high blood sugar, modified low-density lipoproteins (LDL, the "bad cholesterol"), physical stress from high blood pressure, or chemical insult from tobacco smoke. Now nicotine itself appears to remodel key structures in a way that primes and enhances the invasion of smooth muscle lining the vessel wall.

Identifying a possible nicotine-posodome link in the invasion step of plaque formation process suggests a new means of intervening in the process: targeting the cell structures that are changed by nicotine and that promote invasion of the smooth muscle lining the vessel wall. If a therapy could prevent, slow, or reverse that step, it would likely interrupt the plaque-production cycle.

Fatty deposits accumulate in blood vessels beginning as young as age 10 and progress over a person's lifetime. Heart disease results if the deposits continue to build and harden into vessel-clogging plaque. When plaque ruptures, it can block blood flow, starving the heart or brain of oxygen and leading to a heart attack or stroke.

The presentation, "Cigarette smoke and nicotine-induced remodeling of actin cytoskeleton and extracellular matrix by vascular smooth muscle cells," is at 1:45 p.m. on Sunday, Feb. 26, 2012, in the San Diego Convention Center, Hall FGH. ABSTRACT: http://tinyurl.com/73e836j

Lab Studies Raise Flags About New Alzheimer's Drugs

2012-02-22T23:30:00.002-06:00

I know this is specifically about Alzheimers but the article talks about axonal development and targeting which I think are extremely important in neuroplasticity and neurogenesis.
http://www.medpagetoday.com/Neurology/AlzheimersDisease/31255?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g424561d0r&userid=424561&email=oc1dean@yahoo.com&mu_id=

An enzyme that drives plaque formation in Alzheimer's disease also has a key role in normal axonal development and targeting, which might be disrupted by a new class of drugs that inhibit the enzyme, studies in mice suggested.

Animals with a genetically engineered deficiency in the enzyme BACE1 produced offspring with mistargeted olfactory sensory neuron axons, indicating defective axon guidance.

As compared with wild-type mice, the enzyme-deficient offspring had smaller olfactory bulbs that often had malformed glomeruli with randomly oriented, poorly bundled olfactory sensory neuron axons, according to a report published online in Molecular Neurodegeneration.

The findings suggest that newly developed BACE1 inhibitors might disrupt neuronal function and possibly worsen the memory impairment the drugs were designed to treat.

"Let's proceed with caution," Robert Vassar, PhD, of Northwestern University in Chicago, said in a statement. "We have to keep our eyes open for potential side effects of these drugs."

Vassar headed a team of researchers that discovered BACE1 and uncovered its role in amyloid plaque formation, a hallmark finding in the brains of Alzheimer's patients. The observations helped fuel ongoing research and development of BACE1 inhibitors for treatment of Alzheimer's disease.

Aside from the link to amyloid plaque, little was known about BACE1 function. BACE1-deficient mice exhibit hippocampus-based memory deficits, have abnormal EEG findings, and are prone to seizures, Vassar and co-authors wrote. Hypomyelination is another characteristic of mice with genetically engineered enzyme deficiency.

The finding that BACE1 co-localizes with presynaptic neuronal markers has indicated that the enzyme has a role in the development and function of axons or terminals. Studies have also indicated that axon guidance molecules might be targets of BACE1, suggesting a possible role for the enzyme in axon guidance.

To learn more about BACE1 function, investigators studied mice that are homozygous for BASE1 deficiency. Specifically, they examined the role of BACE1 in axon guidance of olfactory sensory neurons, a well-established model of axon targeting.

The highest levels of BACE1 in the olfactory bulb are found in the olfactory sensory neuron axon terminals in glomeruli, suggesting a role for the enzyme.

Subsequent studies revealed several key findings, which were reported simultaneously at the American Association for the Advancement of Science meeting in Vancouver. As compared with wild-type animals, BACE1-deficient mice had:

Smaller olfactory bulbs that weighed significantly less than those of wild-type animals (P=0.00856), suggesting perturbed olfactory sensory neuron axon guidance.
Diminished visual clarity of olfactory sensory neuron axon bundles and glomeruli under magnification, suggesting abnormal organization or structure of axons.
Axon guidance defects in olfactory sensory neurons that expressed specific odorant receptors.

Taken together, the results strongly implied that BACE1-deficient mice had olfactory systems that were "poorly wired."

"It's like a badly wired house," said Vassar. "If the electrician doesn't get the wiring pattern correct, our lights won't turn on and the outlets won't work."

The observed defects in the olfactory system of the enzyme-deficient mice probably originates in the brain, quite possibly the hippocampus, Vassar continued. If true, the hippocampus would be particularly vulnerable to BACE1 inhibition, which might induce and perpetuate disruption of axon guidance.

"It's not all bad news," Vassar said. "These BACE1 blockers might be useful at a specific dose that will reduce the amyloid plaques but not high enough to interfere with the wiring. Understanding the normal function of BACE1 may help us avoid potential drug side effects."