A novel therapeutic target for recovery after stroke

Shit this just sounds like the combination of three already known theories of the

neuronal cascade of death.

Or maybe you want to read about this research way back in September 1999?

The Role of Diaschisis in Stroke Recovery March 2018

 

Now we just need our non-existent stroke leadership to get research going to solve these neuron killer processes. That will never occur. WE HAVE NO STROKE LEADERSHIP!

1. Capillaries that don't open due to pericytes  

2. glutamate poisoning
 

3. excitotoxicity

The latest here:

A novel therapeutic target for recovery after stroke

by Institute for Basic Science

Stroke affects not only the brain areas where the blood supply is interrupted or reduced (infarct), but also other distal areas (diaschisis). The researchers studied mouse brains and found that diaschisis is due to the excessive production of the neurotransmitter GABA and that the administration of KDS2010 combined with rehabilitation can improve motor function after stroke. Credit: IBS

Researchers at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS), Gwangju Institute of Science and Technology (GIST), and Korea Institute of Science and Technology (KIST) have discovered a new mechanism to explain the effects of subcortical strokes and a new possible therapeutic approach.

Every year, 15 million people worldwide suffer from stroke according to the World Health Organization. Five million of those die and another five million are permanently disabled. Stroke is one of the most commonly reported causes of death and greatly impacts patients' quality of life. However, despite its prevalence and negative impact, there are no direct medical treatments for recovery after stroke and patients rely on rehabilitation.
A stroke occurs when the blood supply is interrupted or reduced due to bleeding or occlusion of blood vessels in some part of the brain. Brain cells subsequently begin to die within minutes, causing a regional brain damage. In addition, the stroke leads to a loss of function, called diaschisis, in other brain regions connected to the damaged area. Proposed 115 years ago, diaschisis worsens symptoms and prognosis of stroke patients. However, despite broad clinical interest, diaschisis' molecular and cellular mechanisms are still unknown.
In this study, the researchers reported that diaschisis in the cortex of the mouse brain with subcortical stroke is caused by the decline of neuronal activity, due to the reduction in neuronal glucose uptake. They showed that this is dependent on pathological changes of astrocytes, the most abundant cell type in the brain. "Astrocytes respond to the presence of any chemical disregulation, caused by stroke. They become reactive, proliferate and increase in size," says C. Justin Lee, Director of the Cognitive Glioscience Group, at the IBS Center for Cognition and Sociality and co-corresponding author of this research. The researchers discovered that reactive astrocytes synthesize and release an excessive amount of GABA, an inhibitory neurotransmitter, that affects the activity of neighboring motor neurons.

Targeted Myosin-2 Inhibition Improves Brain Regeneration After Stroke by Relaxing Hypoxia-Induced Vasoconstriction in Capillaries

So this seems to solve 1 of 5 neuronal cascade of death issues.  What the fuck is your hospital doing to solve the other 4? What research are they initiating? Or supporting?

Capillaries that don't open due to pericytes

The 5 causes of the neuronal cascade of death in the first week.

 

Targeted Myosin-2 Inhibition Improves Brain Regeneration After Stroke by Relaxing Hypoxia-Induced Vasoconstriction in Capillaries

• Mate Penzes
• Demeter Turos
• Mate Winternitz
• 
  
• Anna Á. Rauscher
• Mate Gyimesi
• Andras Malnasi-Csizmadia
• Show all authors

DOI:https://doi.org/10.1016/j.bpj.2019.11.2439

Smooth muscle myosin-2 (SMM) is the key regulator of capillary blood flow in the brain tissue. Pre-capillary contractile pericytes (smooth muscle cells, SMCs) block the entrance of brain capillaries in answer to hypoxia during ischemic stroke. One of the major obstacles in stroke therapies is that SMCs remain permanently contracted even after removing the blood clot from large arteries, which hinders healthy blood reperfusion of the infarcted brain regions. Thus, SMM could be an optimal target to improve brain regeneration after clinical interventions. Therefore, we developed an intra-arterial catheter mediated targeted administration of SMM inhibitors into the ischemic brain regions and tested their effects on cerebral blood flow (CBF) after transient middle cerebral artery occlusion (tMCAO) on rats. SPECT and MRI analyses confirmed that different types of SMM inhibitors (e.g. MPH-222) could drastically improve CBF in the ischemic brain areas. We also corroborated this vasodilatation effect on ex vivo human arterioles, where SMM inhibitors could fully relax contracted vessels even in the presence of upstream vasonstrictor signals. Moreover, MPH-222 could also induce neurite outgrowth in different types of neurons through its effect on the non-muscle myosin-2 (NM2) isoforms. These results suggest that targeted, non-selective myosin-2 inhibition is a conceptually new therapeutic way in stroke interventions, which could be combined with current blood clot removing methods (thrombectomy and thrombolysis).

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Innovative technique to examine blood vessels in 3D help unlock secrets of the brain

With this we should be able to watch and see if interventions to stop pericytes from strangling capillaries post-stroke actually work. Or even just to see how long the strangling occurs.  But with NO strategy and NO leadership, solving this part of the neuronal cascade of death will never occur.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=171345&CultureCode=en

• Blood vessels examined in 3D allow scientists to examine circulation in the brain giving greater understanding of how dementia, brain cancer and stroke may affect veins and capillaries in this important organ.
• Technique could identify early warning signs of diseases helping to save lives.
• Scientists previously unable to study minute blood vessels which could unlock secrets of circulation and how diseases form in brain.

A study published today in the Journal of Anatomy has made an important breakthrough in the examination of blood vessels in the brain giving scientists a clearer understanding of how dementia, brain cancer and stroke can affect veins and capillaries in this organ.
Working collaboratively researchers from the University of Surrey and the Federal University of Sao Paulo developed an innovative technique to examine and quantify blood vessels in the brain using 3D Image Analysis (Stereology) procedures.
Using experimental animal models, this technique will allow scientists to study how such diseases develop in the brain and help them identify, through examination of blood vessels, potential warning signs of illnesses before symptoms appear. These learnings can potentially be translated into humans and help reduce the number of deaths from these illnesses.
The procedure can also be used in post mortems and biopsies examinations of animal and human tissue making it easier for pathologists to determine causes of death and quickly identify alterations in the brain circulation (such as clots) or tumors.
The inexpensive technique of dissolving China Ink with gelatin creates a solution making blood vessels more visible with the use of a confocal microscope. This enables scientists and pathologists to make an accurate reading of their number, length, surface area and create 3D images which can help identify changes in their shape and size, key indicators of a number of circulation-related diseases of the brain.
This innovative method will also facilitate a greater understanding of how exercise affects the brain. Scientists will now be able to examine circulatory effects of increased or decreased heart rate, arterial pressure on the brain and the creation of new vessels (angiogenesis).
Co-author of the study Dr Augusto Coppi from the University of Surrey said: “The brain is a fascinating organ but our full understanding of its circulation is lacking. Previously we have been unable to fully sample and perform a quantification of the circulation of the brain in 3D as we simply could not see all vessels due to their minute size and sometimes due to their irregular spatial distribution.
“This new technique will allow us to sample, image and count blood vessels in 3D giving us a greater mechanistic comprehension of how the circulation of the brain works and how brain diseases such as dementia and stroke affect this organ. With an estimated 850,000 people diagnosed with dementia in England, this technique marks a significant breakthrough in the fight against this disease.”

Acute Ischemic Stroke Treatment, Part 2: Treatment “Roles of Capillary Index Score, Revascularization and Time”

More bloviating and talking about what they don't know. You're fucking screwed if you have a stroke right now. The authors need to read up on the neuronal cascade of death. They wouldn't be allowed to receive any funding from my organization with that lack of knowledge.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00117/full?

Firas Al-Ali¹*, John J. Elias² and Danielle E. Filipkowski²

• ¹Department of Neuro Interventional Surgery, Akron General Medical Center, Akron, OH, USA
• ²Department of Research, Akron General Medical Center, Akron, OH, USA

Due to recent results from clinical intra-arterial treatment for acute ischemic stroke (IAT-AIS) trials such as the interventional management of stroke III, IAT-AIS and the merit of revascularization have been contested. Even though intra-arterial treatment (IAT) has been shown to improve revascularization rates, a corresponding increase in good outcomes has only recently been noted. Even though a significant percentage of patients achieve good revascularization in a timely manner, results do not translate into good clinical outcomes (GCOs). Based on a review of the literature, the authors suspect limited GCOs following timely and successful revascularization are due to poor patient selection(wrong, wrong, wrong) that led to futile and possibly even harmful revascularization. The capillary index score (CIS) is a simple angiography-based scale that can potentially be used to improve patient selection to prevent revascularization being performed on patients who are unlikely to benefit from treatment. The CIS characterizes presence of capillary blush related to collateral flow as a marker of residual viable tissue, with absence of blush indicating the tissue is no longer viable due to ischemia. By only selecting patients with a favorable CIS for IAT, the rate of GCOs should consistently approach 80–90%. Current methods of patient selection are primarily dependent on time from ischemia. Time from cerebral ischemia to irreversible tissue damage seems to vary from patient to patient; so focusing on viable tissue based on the CIS rather than relying on an artificial time window seems to be a more appropriate approach to patient selection.

Introduction

The interventional management of stroke (IMS) III trial (1) showed non-superiority of intra-arterial (IA) revascularization combined with intra venous (IV) tissue plasminogen activator (tPA) treatment over IV tPA alone, and the systemic thrombolysis for acute ischemic stroke (SYNTHESIS) trial demonstrated similar lack of favorable clinical outcomes for IA versus IV tPA therapy (2). This is despite the high revascularization rate in the IA arms in these trials. The role of intra-arterial treatment for acute ischemic stroke (IAT-AIS) has been contested. Paradoxically, however, the benefit of revascularization to clinical outcomes is convincingly attested to in prior literature. In a recent meta-analysis of 998 patients with clinical follow-up at 3 months, good clinical outcome was found in 58% of revascularized patients as compared to 24.8% in non-revascularized patients (3). When revascularization occurred within the first 6 h, good clinical outcomes (GCOs) were found in 50.9% of revascularized patients as compared to 11.1% in non-revascularized patients. Other authors reached similar conclusions. Even in the IMS III trial, better revascularization using the modified thrombolysis in cerebral infarction (mTICI) score led to better outcomes than those for patients who achieved lesser revascularization (1). This data were recently resolved with the publication of newer trials. In MR CLEAN, EXTEND-IA, and ESCAPE, good recanalization rates were achieved in 58.7, 86, and 72.4% of patients, respectively, with accompanying GCO rates at 32.6, 71, and 53%, respectively (4–6). While these results demonstrate IA superiority with higher recanalization rates than with IVT, there are still a significant number of patients who achieved good and timely revascularization that did not also achieve GCOs. So if better revascularization improves outcome and IA treatment has a better revascularization rate than IV treatment, how can we explain the lack of GCOs in some of these patients?

Revascularization and Outcome

Revascularization is defined as the restoration of anterograde blood flow to the ischemic area through the recently occluded artery. Currently, this is reported using the mTICI score, with mTICI of 2b or 3 being considered successful revascularization (7). The aim of revascularization is to produce clinical improvement through restoring the cerebral blood flow (CBF) level to greater than the critical threshold of 23 ml/100 g/min of viable brain tissue (8). This should translate into a permanent resolution of AIS symptoms by saving the ischemic tissue before it progresses to irreversible damage. So if perfect revascularization is achieved (mTICI = 3) in a timely manner, i.e., before ischemia becomes irreversible, clinical improvement should be achieved for almost all patients, as well as for the majority of patients with less effective revascularization (mTICI = 2b). However, review of the literature reveals that only around 50% of patients in whom we obtained timely recanalization (mTICI 2b, 3) will achieve a good clinical outcome (Table 1) (1, 2, 9–13). Attempting to solve the paradox regarding why all technically successful revascularizations do not translate into GCOs should help us improve our revascularization strategy.

more at link.

Decoding the Brain’s “Low Fuel” Signal

This blogger pretty much just repeats what I've been saying for years. Pericytes clamping down on capillaries are one of the causes of the neuronal cascade of death. 
What precisely is your doctor doing to stop that problem?
http://knowingneurons.com/2014/05/14/decoding-the-brains-low-fuel-signal/

Brain Power: McCallie teen awarded patent for revolutionary stroke treatment design

Great idea. But once again proving that stroke medical personnel  don't even know that a ton of neurons  keep dying after circulation is restored. Its almost as if they have never heard of the neuronal cascade of death. From 2009. Would you see any other doctor that is 4 years out-of-date?
http://timesfreepress.com/news/2013/nov/30/brain-power/ 
Christian's device prototype also uses a catheter-into-artery approach, but instead aims to drill through the clot before any attempt to remove it is made. Once through, it can supply the barren, neglected side of the artery with direly needed blood flow in as little as five minutes.

But is this just showering the downstream arteries and capillaries with debris? 

Coffee may help perk up your blood vessels

Does this mean you should get coffee immediately after your stroke to get those brain capillaries working better? What does your doctor think? Does your doctor think at all?

 
Coffee may help perk up your blood vessels

The caffeine in a cup of coffee might help your small blood vessels work better, according to research presented at the American Heart Association’s Scientific Sessions 2013.
A study of 27 healthy adults showed – for the first time – that drinking a cup of caffeinated coffee significantly improved blood flow in a finger, which is a measure of how well the inner lining of the body’s smaller blood vessels work. Specifically, participants who drank a cup of caffeinated coffee had a 30 percent increase in blood flow over a 75-minute period compared to those who drank decaffeinated coffee.
“This gives us a clue about how coffee may help improve cardiovascular health,” said Masato Tsutsui, M.D., Ph.D., lead researcher and a cardiologist and professor in the pharmacology department at the University of the Ryukyus in Okinawa, Japan.
The study adds to a growing body of research about coffee, the most widely consumed beverage worldwide.  Previous studies showed that drinking coffee is linked to lower risks of dying from heart disease and stroke, and that high doses of caffeine may improve the function of larger arteries.
Study participants were people who did not regularly drink coffee, ranging in age from 22 to 30. On one day, each participant drank one five-ounce cup of either regular or decaffeinated coffee. Then researchers measured finger blood flow with laser Doppler flowmetry, a non-invasive technique for gauging blood circulation on a microscopic level. Two days later, the experiment was repeated with the other type of coffee. Neither the researchers nor the participants knew when they were drinking caffeinated coffee.
The researchers noted blood pressure, heart rate, and vascular resistance levels. They also took blood samples to analyze levels of caffeine and to rule out the role of hormones on blood vessel function.
Compared to decaf, caffeinated coffee slightly raised participants’ blood pressure and improved vessel inner lining function. Heart rate levels were the same between the two groups.
It’s still unclear how caffeine actually works to improve small blood vessel function, although Tsutsui suggests that caffeine may help open blood vessels and reduce inflammation.
“If we know how the positive effects of coffee work, it could lead to a new treatment strategy for cardiovascular disease in the future,” said Tsutsui.
Co-authors are Katsuhiko Noguchi, Ph.D.; Toshihiro Matsuzaki, M.D., Ph.D.; Mayuko Sakanashi, Ph.D.; Naobumi Hamadate, Ph.D.; Taro Uchida; B.Sc.; Mika Kina-Tanada, D.D.S.; Haruaki Kubota,
M.D.; Junko Nakasone, Ph.D.; Matao Sakanashi, M.D., Ph.D.; Fumihiko Kamezaki, M.D., Ph.D.;
Akihide Tanimoto, M.D., Ph.D.; Nobuyuki Yanagihara, Ph.D.; Yusuke Ohya, M.D., Ph.D.; Hiroaki Masuzaki, M.D., Ph.D.; and Shogo Ishiuchi, M.D., Ph.D.
Author disclosures are on the abstract.

How Blood Vessels Regroup After Stroke

You will need to followup with your doctor to push this to a stroke protocol ready in time for your next stroke.  Or do you think your doctor will do anything to prepare for your next stroke? 

How Blood Vessels Regroup After Stroke

By thinking of cells as programmable robots, researchers at Rice University hope to someday direct how they grow into the tiny blood vessels that feed the brain and help people regain functions lost to stroke and disease.

---

Rice bioengineer Amina Qutub and her colleagues simulate patterns of microvasculature cell growth and compare the results with real networks grown in their lab. Eventually, they want to develop the ability to control the way these networks develop.
The results of a long study are the focus of a new paper in the Journal of Theoretical Biology.
"We want to be able to design particular capillary structures," said Qutub, an assistant professor of bioengineering based at Rice's BioScience Research Collaborative. "In our computer model, the cells are miniature adaptive robots that respond to each other, respond to their environment and pattern into unique structures that parallel what we see in the lab."
When brain cells are deprived of oxygen -- a condition called hypoxia that can lead to strokes -- they pump out growth factor proteins that signal endothelial cells. Those cells, which line the interior of blood vessels, are prompted to branch off as capillaries in a process called angiogenesis to bring oxygen to starved neurons.
How these new vessels form networks and the shapes they take are of great interest to bioengineers who want to improve blood flow to parts of the brain by regenerating the microvasculature.
"The problem, especially as we age, is that we become less able to grow these blood vessels," Qutub said. "At the same time, we're at higher risk for strokes and neurodegenerative diseases. If we can understand how to guide the vessel structures and help them self-repair, we are a step closer to aiding treatment."
First, they need to understand how individual cells respond to stimuli. To model the process in a computer requires rules, Qutub said. In these simulations, each cell is a "state machine," a unit that goes from one "state" to the next in time based on input. In the case of these endothelial cells, the input comes from vascular endothelial growth factor and/or brain-derived neurotrophic factor, proteins that encourage angiogenesis.
"There's a memory in each of these cells that helps define how they emerge into these very elaborate vasculature structures," she said. The cells that quickly differentiate into tip and stalk cells follow particular rules to advance, grow, divide and branch, depending on input from growth factors and from neighboring cells that can dictate how far and how fast they develop.
For instance, she said, in a chain of endothelial cells, a tip cell at its maximum length can only continue to migrate if the stalk cell immediately behind grows and pushes it forward. Similarly, the team set rules for branching and changes in direction, as well as an "idle" state, all based on observation of real vessel growth.
The researchers modeled a set of endothelial cells growing from a sphere and exposed them to simulated growth factors. They let them grow for what, in real life, would be a period of 24 hours, but in the computer took fractions of a second. They ran tens of thousands of simulations to see how the cells would migrate, proliferate and branch under various conditions.
The next step was to figure out which of the computer simulations matched actual behavior. Qutub's lab cultured spheres of human umbilical vein endothelial cells in collagen scaffolds, exposed them to growth factors and took microscope images as they developed networks over several days.
They compared these images with the simulations. The closest matches -- of which there are only a few amid thousands of simulations -- became the basis for a refined set of rules.
"We know how cells are connected as a function of the growth factors, and there are very distinct patterns to the way these networks are organized," Qutub said. "So when we compare the simulations with the assays, we find parallels that let us classify what we see in the real networks. This gives us a paradigm where we can start to think of actually programming real cells with chemical signaling.
"It opens up a lot of doors," she said. "Now we can think about changing things in the cells or giving them drugs that target pathways and growth factors to induce a particular vasculature structure."
Byron Long, a postdoctoral research associate in the Qutub Group, is lead author of the paper. Co-authors are Rice undergraduates Rahul Rekhi and Jiwon Jung and Amada Abrego, an undergraduate student at the Monterrey Institute of Technology, Mexico, who took part in the Rice Summer Undergraduate Research Program in Biosciences and Bioengineering, funded by the Howard Hughes Medical Institute, and has a complimentary appointment to the Qutub Lab.

Use it or Lose it - stroke rehab

This seems to be one of the golden pillars of stroke rehab. I think everyone is mostly wrong on this.

You are told as soon as the first therapist talks to you that you need to use any movement/sensation you have or you will lose it. They believe it because they see survivors who initially had some movement  and a month or two later that movement is gone. They question the survivor about how often they tried the movement and the response usually is, 'Except for therapy sessions I never tried that movement'. This is correlation not causation. Poor analytical thinking on their part. They are probably thinking about atrophied muscles and their lack of use.

I'll argue that the reason it was lost is that that area was partially damaged; in the penumbra or blood drainage area and the neuronal cascade of death was initiated and neurons died over the next week or so. The initial tries worked because the neurons were still alive and barely functioning.

This just points out the absolute imperative to find out how to stop that death cascade.  177 possibilities here.This can also be the reason that very early therapy does not have a good success rate. Movement regresses for a while until the cascade resolves itself and the surviving neurons start taking on their tasks. This would look like failure on early rehab.

This should be fairly easy to figure out, you can use nanowires to listen in on single neurons or lay a grid across the cortex to listen in.

Some of the causes of those neuron deaths;

1.  Excitotoxicity

2.  Glutamate poisoning

3.  Capillaries that don't open due to pericytes

4.  Inflammatory action leaking through the blood brain barrier

Neuroprotection vs. Neuronal Cascade of Death

If you were an agency funding research and a stroke researcher came to you with a proposal, Which of those words in the title would be more likely to at least get reviewed?  Never ever refer to neuroprotection, thats boring. Words can cause action, use ones that denote urgency. Both refer to the death of neurons that has been set in place by the original stroke. This will occur over the next week or so(at least until someone researches the real timeframe)  Some of the causes of those neuron deaths;
1.  Excitotoxicity
2.  Glutamate poisoning
3.  Capillaries that don't open due to pericytes
4.  Inflammatory action leaking through the blood brain barrier

Your doctor should know about all of these and if we had a Great stroke association pushing this type of research we might get results in 20-30 years.
This is where all the focus of stroke research should be, not tPA. The irrational focus on tPA is preventing something better from being found.
You stop the neuronal cascade of death and I bet we could reduce the 30 day deaths from stroke substantially. Why hasn't someone from the stroke medical world been pushing this? Are they all brain-dead?

ASA - Dr. Sacco, 

NSA - Mr. Baranski, 

WSO - Dr. Stephen Davis

Time is Brain, you know. F.A.S.T.  How many neurons will they let die because of inaction?

For Best Outcomes In Stroke, Near-Complete Blood Flow Restoration Critical

And yet these researchers totally failed to mention opening up capillaries closed due to pericytes. Complete failure. If you know these guys ask how they can miss something so obvious. Pericyte image here
 http://www.medicalnewstoday.com/releases/252294.php
 Two Rhode Island Hospital researchers recently found that restoring near-complete blood flow to the brain is necessary to restore or preserve neurological function following stroke. Seems like a no-brainer, right?

Yet until their research was complete, many physicians and researchers believed that partial blood-flow restoration was good enough. Not anymore.

The study by Mahesh Jayaraman, M.D., director of interventional neuroradiology, and Brian Silver, M.D., director of the Comprehensive Stroke Center at Rhode Island Hospital, is published online in advance of print in the American Journal of Neuroradiology.

The researchers found that when performing intra-arterial stroke therapy - putting a catheter directly into a blood vessel in the brain in an effort to open it - it's simply not enough to open some of the vessels. Rather, opening the vast majority of the vessels is needed to truly restore neurological function in patients with acute ischemic stroke who are ineligible for, or fail to improve following intravenous tissue plasminogen activator (tPA), a common treatment for stroke.

"Stroke caused by a large blockage in the brain is potentially debilitating," Jayaraman said. "But if we can successfully restore blood flow to the majority of the blood vessels in the brain, then we may be able to help reduce the severity of a patient's stroke. While previous studies have shown that any restoration of blood flow can help, our results are the first to show that near-complete restoration is needed to help improve patient outcomes, including the preservation of fine and gross motor skills, speech and behavior."

The purpose of the study was to determine whether the degree of restoration of blood flow to the brain has an impact on the degree of brain damage and clinical outcomes. The study found that there are, in fact, significant differences in clinical outcomes between partial and near-complete blood flow restoration following intra-arterial stroke therapy for strokes that occur in the front part of the brain. As a result, Jayaraman and Silver concluded that future patient care plans should focus on restoring as much blood flow as possible, combining new technologies with a health care infrastructure designed to deliver rapid care.

"Rapid treatment is critical for stroke patients," Silver said. "It's not enough to just open blood vessels to the brain; it has to be done as early as possible. At Rhode Island Hospital, more than 50 percent of our patients are treated with intravenous clot busters (tPA) in less than 60 minutes after arrival, and a significant number of stroke patients are being treated with an intra-arterial therapy in less than two hours from the time they arrive. Stroke treatment needs to evolve, and that includes using new technologies that allow physicians to remove the clot in its entirety as quickly as possible."

Stroke is a leading cause of death in the United States; more than 800,000 people in the U.S. die each year from cardiovascular disease and strokes. Sometimes called a "brain attack," stroke occurs when a clot blocks the blood supply to the brain or when a blood vessel in the brain bursts. If not treated in a timely manner, stroke can cause death or significant disability, such as paralysis, speech difficulties and emotional problems.

Researchers develop neuroimaging technique capturing cocaine's devastating effect on brain blood flow

I'm more interested in the ability to image the small capillaries in the brain. That would allow researchers to determine exactly how, when and what would release the pericytes clamping down on capillaries in the immediate aftermath of a stroke. 
http://medicalxpress.com/news/2012-10-neuroimaging-technique-capturing-cocaine-devastating.html

Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal's October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

Read more at: http://medicalxpress.com/news/2012-10-neuroimaging-technique-capturing-cocaine-devastating.html#jCp

 Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal's October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal's October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

Read more at: http://medicalxpress.com/news/2012-10-neuroimaging-technique-capturing-cocaine-devastating.html#jCp

Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal's October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

Read more at: http://medicalxpress.com/news/2012-10-neuroimaging-technique-capturing-cocaine-devastating.html#jCp

Researchers from the Department of Biomedical Engineering at Stony Brook University have developed a high-resolution, 3D optical Doppler imaging tomography technique that captures the effects of cocaine restricting the blood supply in vessels – including small capillaries – of the brain. The study, reported in Molecular Psychiatry, and with images on the journal's October 2012 cover, illustrates the first use of the novel neuroimaging technique and provides evidence of cocaine-induced cerebral microischemia, which can cause stroke.

Read more at: http://medicalxpress.com/news/2012-10-neuroimaging-technique-capturing-cocaine-devastating.html#jCp

Microvascular Repair: Post-Angiogenesis Vascular Dynamics

This is something we need to have a complete understanding of if we ever expect to create functioning neurons in our dead areas. And determine how to open up the micro-capillaries that close due to pericytes in the immediate aftermath of the stroke.
http://onlinelibrary.wiley.com/doi/10.1111/j.1549-8719.2012.00207.x/abstract

Abstract

Vascular compromise and the accompanying perfusion deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures thereby establishing more competent microcirculatory beds. Growing evidence indicates that an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation and includes vascular guidance and inosculation, vessel maturation, pruning, arterio-venous specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation. While many of the mechanisms regulating angiogenesis have been detailed, a thorough understanding of the mechanisms driving post-angiogenesis activities specific to neovascularization has yet to be fully realized, but is necessary in order to develop effective therapeutic strategies for repairing compromised microcirculations as a means to treat disease.

Astrocytes build blood vessel scaffolds for long distance neuron migrations

You'll have to read this blogger at the url. Signalling to get migrating neurons to the correct place. Hey, we should be able to mimic this and get new neurons to the damaged areas. Tell your researcher about this. This could be really wonderful for all us chronic survivors.
http://www.guardian.co.uk/science/neurophilosophy/2012/feb/02/1
Star-shaped cells called astrocytes build blood vessel highways for migrating neurons.
The journey undertaken by newborn neurons in the adult mouse brain is like the cellular equivalent of the arduous upstream migration of salmon returning to their hatching river. Soon after being born in the subventricular zone near the back of the brain, these cells embark on a long-distance migration to the front-most tip of the brain. Their final destination – the olfactory bulb – is the furthest point from their birth place, and they travel two-thirds of the length of the brain to get there.
Several years ago, a team of researchers from Canada showed that the pathway for this migration – called the rostral migratory stream – is lined with a scaffold of capillaries, and that the young cells crawl along the blood vessels during their journey. In a follow-up study, they now report that the construction and organization of the blood vessel scaffold is orchestrated by star-shaped cells called astrocytes.

Bidirectional control of CNS capillary diameter by pericytes

A good explanation of capillary action. Make sure your neurologist can answer your questions about how to get your brain capillaries working after a stroke. Don't take, 'I don't know/no clue', for an answer. Never mind me, I have no medical training so I can't say anything useful about how the medical world doesn't know what it is doing in regard to stroke rehab. Naked emperor and all.

Bidirectional control of CNS capillary diameter by pericytes

Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques^{1, 2, 3}. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles⁴, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles^{5, 6}, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins⁷, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at 2 m s^-1 to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.

New artery blockage treatment may be in the offing

This would have been useful to me if I would have known I had plaque in my arteries.
http://www.medcitynews.com/2012/01/new-artery-blockage-treatment-may-be-in-the-offing/?utm_source=rss&utm_medium=rss&utm_campaign=new-artery-blockage-treatment-may-be-in-the-offing
Artery blockage treatments, especially as it relates to peripheral artery disease and atherosclerosis, are generally invasive treatments that require catheters, stents and the like.

Now a very early stage Minnesota company, which has licensed technology from the University of Minnesota, is aiming to change the paradigm.

International Cardio Corp. wants to use High Intensity Focused Ultrasoundtechnology to treat PAD noninvasively. The technology adapts ultrasound imaging technology giving it the ability to generate heat and that heat can then be applied directly to the blood in the capillary that feeds the plaque, explains CEO Dennis Sellke. When that heat is applied, it raises the temperature of the blood to 60 degrees Celsius (140 degrees Fahrenheit), thereby killing the tissue in the lesion by starving it of its “nutrient source.”

Unlike, ablation techniques, which also uses heat, there is no issue of tissue charring, Sellke declared.

The technology was developed by Emad Ebbinni, a professor in the University of Minnesota’s Electrical and Computer Engineering department. Sellke replaced Donald Knight as CEO in mid-2011. He is the only employee of the company.

Currently, International Cardio is conducting animal research trials at the University of Minnesota and is using $300,000 it has just raised in seed capital to fund that enterprise. Sellke hopes to raise another $200,000 in the seed round.

Sellke said that the technology could just be added to existing ultrasound equipment and would not require a lot of money to commercialize. But he didn’t specify how much money he was hoping to raise if the animal studies demonstrated the technology’s efficacy.

The benefits, if this technology were to succeed and be commercialized, appears to be in the realm of early intervention. Invasive procedures like angioplastyare typically prescribed to people whose arteries are 70 percent or more occluded, Sellke said. But there are those whose arteries are not as severely blocked, but they are not treated for several years. And that’s where International Cardio could make a difference.

“This technology would be a complement to existing treatments,” Sellke said.

But what about replacing those treatments completely? Sellke said that it “takes time to alter the standard of care,” especially if the outcomes are as good as they are in the case of stents and angioplasty. And there are other issues of reimbursement and getting the product through regulatory approvals that often stand in the way of wide adoption.

But Sellke is not too preoccupied with either the regulatory environment or reimbursement issues. Those are to be contended with later. Currently, Sellke is focused on completing the animal testing, which he believes will be done in the first half of the year.

We are at the research level,” he said, signaling that other product-specific issues will be handled in the second half of 2012.

Presentations from the just completed Neuroscience 2011

Studies highlight the brains resiliency to damage
Presentations from the just completed Neuroscience 2011 show some fascinating possibilities for stroke recovery. None of these will help us directly but for future strokees, if enough research is done there may be some hyperacute therapies.
Previous studies, led by Ron Frostig, PhD, of the University of California, Irvine, found that anesthetized rats undergoing an ischemic stroke could be protected from brain damage if they received sensory stimulation within two hours of stroke onset. The current study found rats were also fully protected if immediately awakened from anesthesia after ischemic stroke and placed in an “enriched environment” replete with buried treats, tunnels, and toys.
http://www.sfn.org/siteobjects/published/0000BDF20016F63800FD712C30FA42DD/7EEDCCFAE51E16A50C47ADCDB808E614/file/Brain%20Repair%20Release%20Final%20Draft.pdf
This does contradict what Jill Bolte-Taylor did to recover from her stroke, she went into shutdown mode with overstimulation.

This one is weird, it seems to say that small blood clots in capillaries can be enveloped and pushed out thru the walls. Great picture at the link.
http://www.ncbi.nlm.nih.gov/pubmed/20505729
The picture shows pericytes which are suspected of not opening up the small capillaries even after the main arteries are cleared via tPA. This becomes one of the problems in the neuronal cascade of death.
Pericytes talked about here:
Even after a clot is gone, about half of capillaries remain constricted—at least in mice—even though blood flow is restored in larger vessels. Researchers have found that free radicals in blood vessels lead to this constriction.
http://www.dana.org/news/brainwork/detail.aspx?id=23436

Continuous Measurement of Cerebral Cortical Blood Flow by Laser-Doppler Flowmetry in a Rat Stroke Model

The first thing I thought about when reading this was that this would be the perfect tool to determine if the suggested drugs for opening pericyte constriction of capillaries actually work.
http://www.nature.com/jcbfm/journal/v9/n5/abs/jcbfm198984a.html

Abstract

Summary: Laser-Doppler flowmetry (LDF), a new method allowing instantaneous, continuous, and noninvasive measurements of microcirculatory blood flow in a small tissue sample, was evaluated for its accuracy in monitoring regional cerebral blood flow (rCBF) in the cortical microcirculation after focal cerebral ischemia. Wistar and spontaneously hypertensive rats (SHR, n = 19) were subjected to permanent occlusion of the middle cerebral and common carotid arteries. Absolute rCBF in a tissue sample of the ischemic hemisphere was measured autoradiographically with [¹⁴C]iodoantipyrine as a tracer and compared to rCBF measured by LDF. Additionally, the percent change in rCBF between baseline and ischemic values was compared for both methods. Absolute rCBF values recorded with LDF correlated poorly (r = 0.54) with [¹⁴C]iodoantipyrine measurements. In contrast, LDF readings expressed as a percentage of ischemic vs. preocclusion readings (relative LDF readings) correlated very well (r = 0.91) with the percent change in [¹⁴C]iodoantipyrine measurements. We conclude that LDF does not provide accurate measurements of absolute rCBF values but this method allows accurate measurements of changes in rCBF due to induction of focal cerebral ischemia

Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization

This one is weird, it seems to say that small blood clots in capillaries can be enveloped and pushed out thru the walls. So is this better than the earlier post here on pericytes?
Who is going to test against each other? Time is Brain you know.
http://oc1dean.blogspot.com/2011/09/restoring-capillary-blood-flow-after.html
the new one here:
pictures here from frontiersin.org

http://www.ncbi.nlm.nih.gov/pubmed/20505729

Abstract

Cerebral microvascular occlusion is a common phenomenon throughout life that might require greater recognition as a mechanism of brain pathology. Failure to recanalize microvessels promptly may lead to the disruption of brain circuits and significant functional deficits. Haemodynamic forces and the fibrinolytic system are considered to be the principal mechanisms responsible for recanalization of occluded cerebral capillaries and terminal arterioles. Here we identify a previously unrecognized cellular mechanism that may also be critical for this recanalization. By using high-resolution fixed-tissue microscopy and two-photon imaging in living mice we observed that a large fraction of microemboli infused through the internal carotid artery failed to be lysed or washed out within 48 h. Instead, emboli were found to translocate outside the vessel lumen within 2-7 days, leading to complete re-establishment of blood flow and sparing of the vessel. Recanalization occurred by a previously unknown mechanism of microvascular plasticity involving the rapid envelopment of emboli by endothelial membrane projections that subsequently form a new vessel wall. This was followed by the formation of an endothelial opening through which emboli translocated into the perivascular parenchyma. The rate of embolus extravasation was significantly decreased by pharmacological inhibition of matrix metalloproteinase 2/9 activity. In aged mice, extravasation was markedly delayed, resulting in persistent tissue hypoxia, synaptic damage and cell death. Alterations in the efficiency of the protective mechanism that we have identified may have important implications in microvascular pathology, stroke recovery and age-related cognitive decline.