Stroke Researchers Aim to Stem the “Ischemic Cascade”

What took them so long to figure this out?  How much shouting needs to be done before doctors finally come to an understanding of the basis of where research should go?  Dr.  Moskowitz wrote extensively about this earlier here:

The Science of Stroke: Mechanisms in Search of Treatments Dr. Michael A. Moskowitz

Stroke Researchers Aim to Stem the “Ischemic Cascade”

A stroke may be sudden, but much stroke damage is not. While brain cells completely deprived of blood at the core of an ischemic stroke (the most common kind)  die within minutes, in the broader “penumbra” where circulation is down but not out, the process is gradual—and reversible.
Neuroscientists speak of the “ischemic cascade:” Without the energy from oxygen and glucose required to maintain neurotransmitter storage, neurons release massive amounts of glutamate. The resulting excitotoxicity allows a flood of calcium, sodium, and water into the cell, producing excessive nitric oxide and leading to inflammation, free radical formation, and, ultimately, the death of the cell.
“Cells in the penumbra stay for hours, maybe days in a meta-stable state,” says Michael A. Moskowitz, professor of neurology at Harvard. “They don’t function normally and don’t carry impulses, but they are alive and rescuable.”
The one approved treatment for ischemic stroke, tissue plasminogen activator (tPA), saves brain in the penumbra in the most direct way:  by dissolving the clot and restoring circulation. The drug must  be given within 3-4 hours of symptoms to do any good, though, and restoring circulation can bring problems of its own, including hemorrhage. In practice only 5 percent of patients benefit.
In recent years, researchers have sought to widen the window of therapeutic opportunity by targeting the ischemic cascade itself—halting the destructive process through neuroprotective strategies. Their activity has been intense: More than a thousand compounds have been considered, and more than one hundred tested in clinical trials—but none has yet succeeded. What are they?
 “An enormous amount of energy has been put into this, but no one has hit pay dirt,” says Moskowitz. “It’s been a very bad time for people interested in neuroprotection.” More than the innate difficulty of the problem, he suggests, the failure reflects serious flaws in the science behind screening: “Proof of concept has been lacking for most drugs chosen for clinical trials. They were tested without any demonstration that they could actually get into the brain, bind to their receptors, and do what they were intended to do.”
 On the other hand, poor experimental design may have meant promising possibilities were overlooked. “We may have thrown the baby out with the bathwater in some previous studies,” Moskowitz says.
He emphasizes that this dismal history by no means discredits the concept of neuroprotection. “There shouldn’t be so much doom and gloom. This isn’t an easy business, but there’s no theoretical reason why we can’t do a better job of rescuing cells. We need to reinvent the field.”

A most promising study

Asked about current research, Moskowitz mentioned Michael Tymianski. “He’s a very good, thoughtful investigator. I’d say, from the excitement point of view, [his work] may be the most encouraging thing we’ve seen.”
Tymianski’s research involves the excessive release of glutamate that occurs early in the ischemic cascade, the first step toward catastrophic excitotoxicity. Attempts to abort this process by blocking the NMDA glutamate receptor itself haven’t worked because glutamate neurotransmission is essential to normal neuron function. Tymianski’s approach is more selective: to inhibit a protein, PSD-95, that links the receptor to molecular events within the cell that promote overproduction of nitric oxide and the influx of calcium.
Tymianski, a senior scientist at Toronto Western Research Institute, and his colleagues have been developing a PSD-95 inhibitor for 15 years, testing it in cell cultures and rodent models of stroke. In his most recent study, reported in the March 8 issue of Nature, they administered the compound, Tat-NR2B9, to macaques, non-human primates whose brain closely resemble ours.
Findings were encouraging: the drug reduced the area of brain loss, compared with placebo, when given 1-3 hours after a large cerebral artery was blocked to simulate a stroke. The animals also fared significantly better in tests of neurological function up to two weeks later, confirming that the simulated stroke had done less damage.
“Our results show that neuroprotection is unequivocably feasible in the complex brain,” Tymianski says. “The challenge now is to design a human trial to show clinical benefit.”
The compound has already been shown to be safe in a recent clinical trial in which it was given to patients just after surgery to repair a brain aneurysm, a procedure that carries a high risk of stroke. Although he could not discuss further results in detail, Tymianski called them favorable, suggesting that ischemic damage had been reduced in patients who had strokes after the procedure.
Next, he hopes to test the compound in patients with acute ischemic stroke. Because the drug is apparently safe even in the face of hemorrhagic stroke, it might be given by emergency medical personnel en route to the hospital without the expert screening needed for tPA, dramatically shortening the time to potential neuroprotection. [Tymianski heads a company established to develop the drug in question.]
Tymianski’s success has led researchers to seek other ways to block the PSD-95 pathway. “His work is really impressive, but we like to think we’ve made a better compound,” said Anders Bach, a postdoctoral fellow at University of Copenhagen. The molecule developed by his group has a much higher affinity for PSD-95, and results of a study in mice, published in Proceedings of the National Academy of Sciences in February 2012, suggests that this enhanced its ability to protect the brain.

Other routes to neuroprotection

Researchers elsewhere are addressing other parts of the ischemic cascade.
“In my lab we’ve used two approaches to promote survival in the penumbra,” says Nicolas G. Bazan, director of the Neuroscience Center of Excellence at Louisiana State University and a member of the Dana Alliance for Brain Initiatives. “We’ve devised new molecules that can cross the blood-brain barrier and block bad things happening. And we’ve looked inside the brain to piece out the intrinsic mechanisms that the brain sets in motion to protect itself.”
Much of his research over the past several decades has involved the release of free fatty acids in stroke, with a particular eye toward an endogenous molecule derived from the fatty acid DHA, neuroprotectin-D1, which appears to reduce the impact of ischemia.
A recent focus of his attention has been platelet activating factor (PAF), a compound that normally aids in blood clotting but when released in large amounts by ischemia apparently participates, along with glutamate, in the cascade of excitotoxicity and its consequences.
In a study reported in the March 2012 issue of Translational Stroke Research, Bazan and his colleagues showed that timely administration of a PAF antagonist, LAU-0901, to rats reduced the area of brain damage after experimental stroke, limited inflammation, and improved neuron survival. Animals treated with LAU-0901 showed significantly less behavioral and neurological impairment up to a week later, compared to those given placebo. [Louisiana State University holds the patent on LAU-0901]
Another conspicuously active area of neuroprotection research is hypothermia. Lowering body temperature by just a few degrees appears to slow multiple destructive processes unleashed by ischemia—excitotoxicity, inflammation, free radical release— simultaneously, according to Midori A. Yenari, professor of neurology at University of California, San Francisco.
Hypothermia has been shown to protect the brain against disrupted circulation in conditions other than stroke—it is recommended for resuscitation of cardiac arrest survivors, for example—and animal experiments have been encouraging.
 What’s more, its benefits may persist long after the immediate post-stroke period. “There are a few studies suggesting a positive downstream effect on recovery— when cooling [is initiated] the first day, restorative processes like neurogenesis are improved months later,” Yenari says.
Like other stroke interventions, hypothermia would probably be used along with thrombolytic therapy, but how the two interact remains an open question. “[Some] studies suggest that thrombolysis doesn’t work as well when the brain is cooled, but other research indicates that if  tPA is given, the risk of hemorrhage is reduced,” she says.
The most imposing barriers to hypothermia for acute stroke are practical: Lowering body temperature can induce uncomfortable shivering, disturb electrolyte balance, and raise the risk of pneumonia or cardiac complications, particularly in older patients with other illnesses.
Researchers have used surface cooling, circulating ice water to cool blood vessels internally, and measures like helmets to cool the brain selectively. “People are now trying to identify drugs to cool the body instead of mechanical measures” in hopes of avoiding complications, says Yenari.

Delayed warfarin induced skin necrosis in a patient with poor warfarin metabolizing activity due to interrupted warfarin therapy

I would hope your doctor is telling you about this side effect. I don't like the word necrosis. You'll have to read this at the link since its an image rather than text.
http://resources.metapress.com/pdf-preview.axd?code=y7840271tx4q8715&size=largest
Warfarin-induced skin necrosis (WISN) is a rare but potentially devastating complication of
oral anticoagulation occurring within 3-10 days of warfarin therapy. Potential causes of
WISN include overdose of warfarin, drugs which affect liver function, acquired or

Study Shows Most Commonly Mutated Gene in Cancer may have a Role in Stroke

Get your researcher to follow up on this discovery. It won't help us but could help future strokes.
http://www.newswise.com/articles/study-shows-most-commonly-mutated-gene-in-cancer-may-have-a-role-in-stroke
The gene p53 is the most commonly mutated gene in cancer. p53 is dubbed the “guardian of the genome” because it blocks cells with damaged DNA from propagating and eventually becoming cancerous. However, new research led by Ute M. Moll, M.D., Professor of Pathology at Stony Brook University School of Medicine, and colleagues, uncovers a novel role for p53 beyond cancer in the development of ischemic stroke. The research team identified an unexpected critical function of p53 in activating necrosis, an irreversible form of tissue death, triggered during oxidative stress and ischemia. The findings are detailed online in Cell.

Ischemia-associated oxidative damage leads to irreversible necrosis which is a major cause of catastrophic tissue loss. Elucidating its signaling mechanism is of paramount importance. p53 is a central cellular stress sensor that responds to multiple insults including oxidative stress and is known to orchestrate apoptotic and autophagic types of cell death. However, it was previously unknown whether p53 can also activate oxidative stress-induced necrosis, a regulated form of cell death that depends on the mitochondrial permeability transition pore (PTP) pore.
“We identified an unexpected and critical function of p53 in activating necrosis: In response to oxidative stress in normal healthy cells, p53 accumulates in the mitochondrial matrix and triggers the opening of the PTP pore at the inner mitochondrial membrane, leading to collapse of the electrochemical gradient and cell necrosis,” explains Dr. Moll.
"p53 acts via physical interaction with the critical PTP regulator Cyclophylin D (CypD). This p53 action occurs in cultured cells and in ischemic stroke in mice."

Of note, they found in their model that when the destructive p53-CypD complex is blocked from forming by using Cyclosporine-A type inhibitors, the brain tissue is strongly protected from necrosis and stroke is prevented.

“The findings fundamentally expand our understanding of p53-mediated cell death networks,” says Dr. Moll. “The data also suggest that acute temporary blockade of the destructive p53-CypD complex with clinically well-tolerated Cyclosporine A-type inhibitors may lead to a therapeutic strategy to limit the extent of an ischemic stroke in patients.”
“p53 is one of the most important genes in cancer and by far the most studied,” says Yusuf A. Hannun, M.D., Director of the Stony Brook University Cancer Center, Vice Dean for Cancer Medicine, and the Joel Kenny Professor of Medicine at Stony Brook. “Therefore, this discovery by Dr. Moll and her colleagues in defining the mechanism of a new p53 function and its importance in necrotic injury and stroke is truly spectacular.”

Dr. Moll has studied p53 for 20 years in her Stony Brook laboratory. Her research has led to numerous discoveries about the function of p53 and two related genes. For example, previous to this latest finding regarding p53 and stroke, Dr. Moll identified that p73, a cousin to p53, steps in as a tumor suppressor gene when p53 is lost and can stabilize the genome. She found that p73 plays a major developmental role in maintaining the neural stem cell pool during brain formation and adult learning. Her work also helped to identify that another p53 cousin, called p63, has a critical surveillance function in the male germ line and likely contributed to the evolution of humans and great apes, enabling their long reproductive periods.

Dr. Moll’s Cell study coauthors include: Angelina V. Vaseva and Natalie D. Marchenko, Department of Pathology, Stony Brook University School of Medicine; Kyungmin Ji and Stella E. Tsirka, Department of Pharmacological Sciences, Stony Brook University School of Medicine; and Sonja Holzmann, Department of Molecular Oncology, University of Gottingen in Germany.

About Stony Brook University School of Medicine:
Established in 1971, the Stony Brook University School of Medicine includes 25 academic departments. The three missions of the School are to advance the understanding of the origins of human health and disease, train the next generation of committed, curious and highly capable physicians, and deliver word-class compassionate healthcare. As a member of the Association of American Medical Colleges (AAMC) and a Liaison Committee on Medical Education (LCME) accredited medical school, Stony Brook is one of the foremost institutes of higher medical education in the country. Each year the School trains nearly 500 medical students and over 480 medical residents and fellows. Faculty research includes National Institutes of Health-sponsored programs in neurological diseases, cancer, cardiovascular disorders, biomedical imaging, regenerative medicine, infectious diseases, and many other topics. Physicians on the School of Medicine faculty deliver world class medical care through more than 30,000 inpatient, 80,000 emergency room, and approximately 350,000 outpatient visits annually at Stony Brook University Hospital and affiliated clinical programs, making its clinical services one of the largest and highest quality on Long Island, New York. To learn more, visit www.medicine.stonybrookmedicine.edu.

Study of the Day: Why Crowded Coffee Shops Fire Up Your Creativity

So who is going to take the initiative and study this for stroke survivors? Is this similar to the enriched environment that Dale Corbett refers to here; by Dale Corbett back in Feb. 2011

Study of the Day: Why Crowded Coffee Shops Fire Up Your Creativity

PROBLEM: To optimize creativity, how quiet or noisy should your workspace be?

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• Media Multitaskers May Have Sharper Senses
• Bilingualism May Boost Attention, Working Memory
• Email Breaks at Work Reduce Stress, Improve Productivity

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METHODOLOGY: Researchers led by Ravi Mehta conducted five experiments to understand how ambient sounds affect creative cognition. In one key trial, they tested people's creativity at different levels of background noise by asking participants to brainstorm ideas for a new type of mattress or enumerate uncommon uses for a common object.
RESULTS: Compared to a relatively quiet environment (50 decibels), a moderate level of ambient noise (70 dB) enhanced subjects' performance on the creativity tasks, while a high level of noise (85 dB) hurt it. Modest background noise, the scientists explain, creates enough of a distraction to encourage people to think more imaginatively. (Here's a helpful chart on typical noise levels.)
CONCLUSION: The next time you're stumped on a creative challenge, head to a bustling coffee shop, not the library. As the researchers write in their paper, "[I]nstead of burying oneself in a quiet room trying to figure out a solution, walking out of one's comfort zone and getting into a relatively noisy environment may trigger the brain to think abstractly, and thus generate creative ideas."
SOURCE: The full study, "Is Noise Always Bad? Exploring the Effects of Ambient Noise on Creative Cognition," is published in the Journal of Consumer Research.

Startup tests mesh+microsponges as alternative brain aneurysm treatment

So ask your doctor which option is best for you, watchful waiting, coiling, gluing or this mesh. They should know the efficacy and risks for each treatment. You wouldn't want to listen anything I have to say.
http://medcitynews.com/2012/06/medical-device-startup-seeks-to-provide-alternative-brain-aneurysm-treatment/?utm_source=rss&utm_medium=rss&utm_campaign=medical-device-startup-seeks-to-provide-alternative-brain-aneurysm-treatment

A Minnesota startup is exploring ways to provide a better way to treat brain aneurysms.
A brain aneurysm is a swelling of a blood vessel in the brain with the potential to leak or rupture. There are roughly 3 million to 5 million people with cerebral aneurysms in the U.S.
Aneuclose is pursuing several different approaches, but the one that is furthest along involves a mesh device. The idea is to insert the mesh or net into the sac of the aneurysm, fill up the mesh with microsponges and a contrast media or other liquid. And the hope is for the mesh to expand and take up the space in the irregular shaped aneurysm with the liquid seeping out through the pores of the mesh, while the microsponges are retained. Then the device is closed and detached. The mesh is intended to treat narrow-neck aneurysms.

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“This is exciting because people have tried to seal off aneurysms with stent-like or wire-like things and it’s very hard to get those to conform to an irregular-shaped aneurysm,” said Robert Connor, CEO of Aneuclose, in an interview.With the mesh — called Janjua Aneurysm mesh, after Connor’s partner and co-inventor Dr. Tariq Janjua, medical director, Neurocritical Care Medicine, National Brain Aneurysm Center — and microsponges, this is now conceivable.
Connor has been bootstrapping this invention with three partners who have spent their own money on bench testing. He acknowledges that the company is very early stage and has a long, tough road to hoe, but believes that physicians may warm to the device once he can prove that it can have better outcomes.
There are several standard methods of treating brain aneurysms currently, Connor explained. There is surgical clipping, which is essentially invasive brain surgery where physicians clamp the aneurysm from the outside. But such invasive measures have their own risks, not to mention that it is hard to access aneurysms in certain areas of the brain, Connor said.
Platinum coiling is another standard treatment that uses an endovascular approach to insert flexible coils into the aneurysm from within the blood vessel. Connor said the coils are able to occlude maybe 30 percent to 40 percent of the aneurysm space.
“Sometimes the blood continues to circulate and the aneurysm continues to grow,” Connor said. “Another problem is that coils can occlude into the parent vessel.”
Aside from the clinical issues related to coiling, it is also expensive because the material is platinum. A less expensive alternative is no small matter when trying to get reimbursement for a novel procedure.
Connor said the next step is to do more bench testing and then test the concept in animal models — most likely in rabbits. He expects the bench testing would cost around $50,000 and if all goes well, the animal studies could begin at the end of the summer.
All other challenges aside — ability to show proof of concept, raising capital or getting strategic partners, regulatory uncertainty — a big task will be to convince physicians.
“Physicians are relative conservative and rightly so because if they try something new and it doesn’t work, [there will be] more serious complications than trying a new accounting method.
Still working with Janjua of the National Brain Aneurysm Center gives him confidence.
“Physicians who do coiling and also clipping would be amenable to something better because of the problems with clipping and coiling,” Connor said. “The literature on coiling says that there is a need for a better method.”

Armed for therapy: Baptist's new rehab tool helps upper body

I'm sure there's several of these arm rehabbers that your therapists should have all the data on. So ask them.
http://www.commercialappeal.com/news/2012/jun/20/armed-for-therapy/
Whether it's brushing her hair, lifting a fork or tying her shoelaces, there are hundreds of small, everyday tasks Ella Bledsoe no longer takes for granted.

Mike Brown/The Commercial Appeal

Ella Bledsoe, 69, uses the InMotion Robot with occupational therapist Stacy Castleberry at Baptist Rehabilitation-Germantown.

The 69-year-old stroke patient working to regain control of the muscles on the right side of her body said that after her stroke three months ago, she'd felt like "giving up."
But a new friend at Baptist Rehabilitation-Germantown, a nameless robot, recently acquired by the hospital, has helped her find the strength to keep trying.
During a recent therapy session with the InMotion Arm Robot, Bledsoe played a game similar to "Frogger," moving her right arm back and forth to dodge obstacles raining down on the computer screen in front of her.
"I like this," she said, as she waited for the robot to generate her "score," which is also a progress report for her physical therapist.
Baptist bought the InMotion Arm Robot, at a cost of more than $100,000, about four months ago to supplement care for patients suffering from stroke, cerebral palsy and other neurological conditions.
"This is nice because, traditionally, there are not a lot of tools therapists can use for the upper extremities," said Monika Kolwaite, brain injury coordinator at Baptist Rehab-Germantown.
A therapist might get 50 reps out of a patient during an hourlong session, she said, but the robot gets a thousand. On top of that, the robot tracks a patient's progress and pushes harder each time.
Baptist Memorial Health Care spokeswoman Lori Simpson said the Germantown facility has the only InMotion Arm Robot in the Southeast.
"This is not the only tool in our bag of tricks," said clinical director Amy Barringer. "But this is certainly the newest and has a lot of promise."
Stroke survivors in the U.S. typically undergo rehabilitation therapy in the first six months after a stroke, conventional wisdom being that there's nothing to gain past that point. But a 2010 study published in the New England Journal of Medicine found that arm robot technology coupled with intense rehabilitation could benefit patients five years removed from a stroke.
"What we're seeing is that really recent and remote stroke patients can benefit from this," Barringer said. "It's our hope that patients, who maybe didn't get help years ago, can benefit from the technology we have now."

Swiss company Roche to support stroke research

Every little bit helps. If only the US had initiative like New Zealand.
http://www.odt.co.nz/campus/university-otago/213621/swiss-company-roche-support-stroke-research
University of Otago research, which could eventually boost recovery from strokes, has taken a "huge step forward" through the support of a giant Swiss-based pharmaceutical company, researchers say.
Otago University representatives have signed a contract with Swiss-based firm Roche Pharmaceuticals, and the firm was expected to complete the deal's formalities in a matter of days, researcher Dr Andrew Clarkson said.
"It's a huge step forward in moving it [the potential drug treatment] . . . to the clinic," he said in an interview.
Dr Clarkson, an award-winning research fellow in the Otago departments of psychology and anatomy and structural biology, has been undertaking research that aims to boost recovery from strokes by restoring contact with "silent brain cells".
Some brain cells are killed in strokes, but recent research suggests that some nearby cells previously thought to have also been killed are, in fact, merely "silent".
These cells could potentially be reactivated, helping boost functional recovery.
Physical therapy is often used after strokes, with patients embarking on a "long, hard process" in order to regain some normal limb function.
In a recent study involving mice, published in Nature, Dr Clarkson and colleagues at the University of California found that a drug compound, part of a class of drugs known as "extrasynaptic GABA inverse agonists", could unlock paralysed limbs, with an extra 50% of gross limb motor mobility gained.
But initially, available forms of the drug had needed some further development work to avoid known side effects in the kidneys.
Gaining the backing of the Swiss firm was highly significant, and the firm would be making available for testing a compound which avoided the side effects, researchers said.
Over the next 18 months, Otago researchers would press ahead with further animal-based studies, helping to pave the way for future clinical trials in humans.
Previous clinical trialling of the latest compound, undertaken for other medical applications, meant that more advanced clinical trials could eventually be undertaken much earlier than with a completely new drug, he said.

Meninges: from protective membrane to stem cell niche

This sounds important  but I'll have to leave the full 14 pages to researchers to propose uses for this knowledge.
http://www.ajsc.us/files/AJSC1205003.pdf
Abstract: Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on
meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane.
Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside
the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form
the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the
physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic
stages of cortical development and appear to be necessary for normal corticogenesis and brain structures
formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including
FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural
differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges
of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their
multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on
the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical
distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences
suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be
activated by injury and are able to contribute to CNS parenchymal reaction.

Silent strokes can jeopardize memory

My competent? doctor mentioned something about I must have had several very small strokes because they showed up on the MRI. Of course, he never showed me my locations on the scan or even showed me any scan at all.  No mention on my medical record. Obviously I didn't have either the brains or the need to know about the damage to MY brain. 

Silent strokes can jeopardize memory

The symptoms of a stroke are sometimes obvious, like numbness or weakness on one side of the face, trouble speaking, difficulty walking, and vision problems. Some strokes, though, pass completely unnoticed. But even these can have a significant and lasting effect on memory, reports the June 2012 issue of the Harvard Women’s Health Watch.

These so-called silent strokes create pinpoints of dead cells in the brain. The damaged areas are smaller than with a traditional stroke, and often don’t affect areas of the brain associated with movement or speech.
During a typical ischemic stroke, a blood clot blocks a blood vessel that feeds part of the brain. Without a steady supply of blood, cells in that area malfunction and may die. Symptoms that appear reflect the functions that were controlled by the affected part of the brain. A hemorrhagic stroke caused by a burst blood vessel does the same thing.
During a silent stroke, the interruption in blood flow occurs in part of the brain that doesn’t control any vital functions. Although it doesn’t cause any obvious symptoms—most people who’ve had a silent stroke have no idea it occurred—the damage does show up on an MRI or CT scan.
Silent strokes could interrupt the flow of information in the brain needed for memory, especially if several of these strokes occur over time (which is the most common scenario). Damage from silent strokes can accumulate, leading to more and more memory problems.

Is there anything a woman can do when faced with a stroke that has no symptoms, and that can only be found on an MRI or CT scan? “I think that it should make people aware that it’s imperative to manage risk factors,” says Karen Furie, associate professor at Harvard Medical School and director of the Massachusetts General Hospital Stroke Service. This means:

• controlling blood pressure and diabetes
• not smoking
• keeping cholesterol levels in check
• aiming for a healthy weight
• managing atrial fibrillation

If you are experiencing signs of memory loss, don’t dismiss it as a normal part of aging. See your doctor for testing to make sure the issue isn’t a silent stroke.

University of Southampton and Roke develop technology world first to support stroke patients

We need more of these hand recovery options, everyone else seems to think hand recovery is too hard to work on. Ask your therapist and doctor when this is available for your use.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=121002&CultureCode=en
The University of Southampton, in collaboration with Roke Manor Research Ltd (Roke), a Chemring company, has pioneered the use of Xbox computer technology to develop the world's first process that measures hand joint movement to help stroke patients recover manual agility at home.

The Xbox Kinect works by monitoring whole limb movements allowing controller-free gaming; the gamer becomes the game. However, the University team has taken it a step further to create an algorithm that tracks and measures hand joint angles and the fine dexterity of individual finger movements. The ultimate aim is to capture the data while the patients follow exercises on a TV screen.

The project aims to help people recovering from a stroke to do more regular and precise exercises so that they recover faster. The data collected will be fed back to the therapists caring for the patient so they can continually monitor progress, reducing the need for frequent hospital visits.

This new system has been developed to complement the home-based physiotherapy care already offered to patients in the UK, and follows a recent Stroke Association report[1] which stated that stroke survivors are being denied the chance to make their best recovery because of a lack of post-hospital care.

Health Sciences academic Dr Cheryl Metcalf, at the University of Southampton, has been supervising the project. She comments: "Recovering from a stroke can be a daunting and distressing time for patients and their families. Through our research we know that many people recovering from a stroke find their at-home exercises repetitive and often demotivating. If they are already finding it difficult and frustrating to move their hands, they need something to encourage them to try harder. We wanted to create a more engaging way to help them recover faster. Using the Kinect we have been able to take a commercially available product and develop a highly novel tool that aims to be both cost effective and clinically applicable."

The Southampton and Roke team's next objective is to create a series of computer games to make the rehabilitation process more interesting for the patient. The games will adapt to each individual's ability and help motivate them to reach rehabilitation goals by feeding back higher scores if their joint movements improve.

Simon Wickes, Healthcare Business Sector Manager at Roke, says: "Strokes are the largest single cause of severe disability in the UK and it is estimated that every year half of the 100,000 stroke patients experience upper limb problems. This project could make a significant difference to the wellbeing of those affected.

"As Roke has a strong R&D pedigree in mobile and e-health devices, we were able to provide the technical guidance and support to help the students realise this exciting and valuable project. Not only is it a cost effective out-of-the-box solution, by reducing patient recovery times it could also have a positive impact on the £2.5 billion[2] which the care and rehabilitation of stroke patients cost the UK health and social care system each year."

Therapeutic hypothermia device to prevent brain injury gets a cool $1.5M

More hypothermia stuff.
http://medcitynews.com/2012/06/therapeutic-hypothermia-device-to-prevent-brain-injury-gets-a-cool-1-5m/
An under-wraps Silicon Valley startup that describes itself as “the cold cure for brain injury” has secured $1.5 million in financing.
NeuroSave Inc. CEO Seth Rodgers said the company still has a little ways to go before it can begin talking in detail about its product. But a U.S. Patent and Trademark Office record filed by the company in 2010 refers to a medical apparatus used to induce therapeutic hypothermia by circulating cooling liquid in and around the body through tubes in the esophagus, trachea or pharynx.
Research has found that lowering a patient’s body temperature soon after cardiac arrest or traumatic brain injury can be a way to slow brain cells’ metabolism and prevent life-threatening brain damage. Hypothermia can be induced externally with the use of ice packs or cooling blankets, or invasively through cooling catheters or ice-cold IV saline.
There are a few other companies innovating in this space, including Cryothermic Systems, Life Recovery Systems and BeneChill, a company that’s partnered with Physio-Control and has the CE Mark for a fast-evaporating liquid that cools the brain when it’s squirted up the nose.

Stroke victims respond positively to stem cell treatment - UK

No self-medication here. Ask your doctor first.
http://zeenews.india.com/news/health/diseases/stroke-victims-respond-positively-to-stem-cell-treatment_17449.html
The first set of stroke patients who took part in pioneering stem cell treatment trials have shown signs of improvement, doctors have disclosed.

Six patients, who had human stem cells inserted close to the damaged part of their brain, have since witnessed improvements in the limb weakness that they suffered as a result of their stroke.

In one case, a man who underwent the treatment regained the power of speech after the stem cells of an aborted 12-week-old baby were injected into his brain.

However, doctors have cautioned against reading too much into the early results of the clinical trial, a world first for neural stem cell therapy for stroke victims.

The trial led by Glasgow University neurologist Professor Keith Muir, is being conducted at the Institute of Neurological Sciences at the Southern General Hospital in Glasgow.

“So far we`ve seen no evidence of any harmful effects. We`re dealing with a group of people a long time after a stroke with significant disability and we don`t really expect these patients to show any change over time,” the Telegraph quoted Muir as telling the BBC.

“So it`s interesting to see that in all the patients so far they have improved slightly over the course of their involvement in the study,” he said.

The six patients had suffered strokes between six months and five years before they were treated, and all had been left with limb weakness.

The patients were assessed using the National Institutes of Health Stroke Scale, which ranked the first five patients with a median score of eight before the treatment and four points three months afterwards.

The sixth patient was treated less than three months ago. Six further patients will be treated as part of this Phase 1 trial.

Professor Muir said that he was “intrigued” by the early results of the research.

“We know that if you`re involved in a trial you are going to see patients change in behaviour, particularly if you`re doing something invasive, so we need to be very cautious indeed in interpreting these results,” he said.

“However, that said, it is not something we`d anticipated seeing in this group of patients,” he said.

Further trials are needed to establish whether stem cells actually help the brain repair damaged tissue.

Michael Hunt, chief executive officer of the company developing the treatment, ReNeuron, said that the clinical trial should be considered with caution at this stage.

“The clinical trial is primarily a safety study and we must therefore treat any of the observed early indications of functional benefit with considerable caution at this stage,” he said.

“That said, we remain encouraged by the results seen in the study to date and we look forward to providing further updates,” he added.

Early Menopause May Hold Risk of Brain Aneurysm

Ask your doctor if this is cause or just correlation.
http://www.medpagetoday.com/Neurology/Strokes/33209

stem cell scientist win big technology prize

So our stroke researchers should be able to reuse this process for stem cells.
http://news.yahoo.com/linux-creator-stem-cell-scientist-win-big-technology-164019675.html
US-Finnish software engineer Linus Torvalds, who created the Linux open source operating system, and Japanese stem cell researcher Shinya Yamanaka on Wednesday won a 1.2-million-euro technology prize in Finland.

Yamanaka meanwhile won for "his discovery of a new method to develop induced pluripotent stem cells for medical research," the prize jury said, adding that it was the first time that the award has been split between two scientists.
"Using (Yamanaka's) method to create stem cells, scientists all over the world are making great strides in research in medical drug testing and biotechnology," it said.
"This should one day lead to the successful growth of implant tissues for clinical surgery and combating intractable diseases such as cancer, diabetes and Alzheimer's."
Yamanaka himself vowed in the statement to "continue to work hard to achieve our goals of developing new drugs and medical treatments to intractable diseases by using iPS cell technology."
Finnish President Sauli Niinistoe presented the prize to the two laureates at a ceremony at the Finnish National Opera in Helsinki Wednesday.
The two men shared the prize equally, each receiving 600,000 euros ($751,500).
The Millennium Technology Prize, created in 2002 and funded by the Finnish state and the Technology Academy of Finland, is awarded every two years as a "tribute to developers of life-enhancing technological innovations".

How Brain Performs 'Motor Chunking' Tasks

This is something our therapists should know about in order to help us recover our motor deficits. I would expect a therapy protocol to come from this research.
http://www.sciencedaily.com/releases/2012/06/120612144811.htm
You pick up your cell phone and dial the new number of a friend. Ten numbers. One. Number. At. A. Time. Because you haven't actually typed the number before, your brain handles each button press separately, as a sequence of distinct movements.

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After dialing the number a few more times, you find yourself typing it out as a series of three successive bursts of movement: the area code, the first three numbers, the last four numbers. Those three separate chunks allow you to type the number faster, and with greater precision. Eventually, dialed often enough, the number is stored in your brain as one chunk. Who needs speed dial?
"You can think about a chunk as a rhythm," said Nicholas Wymbs, a postdoctoral researcher in UC Santa Barbara's Department of Psychological and Brain Sciences, and the lead author of a new study on motor chunking in the journal Neuron, published by Cell Press. "We highlight the two-part process that seems to occur when we are chunking. This is demonstrated by the rhythm we use when typing the phone number: rapid bursts of finger movements that are interspersed by pauses."
The rhythm is the human brain taking information and processing it in an efficient way, according to Wymbs. "On one level, the brain is going to try to divide up, or parse, long sequences of movement," he said. "This parsing process functions to group or cluster movements in the most efficient way possible."
But it is also in our brain's best interest to assemble single or short strings of movements into longer, integrated sequences so that a complex behavior can be made with as little effort as possible. "The motor system in the brain wants to output movement in the most computational, low-cost way as possible," Wymbs said. "With this integrative process, it's going to try to bind as many individual motor movements into a fluid, uniform movement as it possibly can."
The two processes are at odds with each other, and it's how the brain reconciles this struggle during motor learning that intrigues Wymbs and the study's other authors, including Scott Grafton, professor of psychology and director of the UCSB Brain Imaging Center. "What we are interested in is functional plasticity of the brain -- how the brain changes when we learn actions, or motor sequences as we refer to them in this paper," Wymbs said.
The study was conducted using human subjects in the Magnetic Resonance Imaging (MRI) scanner in the Brain Imaging Center. The experiment involved three days of training with people performing and practicing three separate motor sequences for up to 200 trials each during the collection of functional MRI data. The subjects were all right-handed but they were asked to learn the sequences using the four fingers of their left hands. Participants practiced the sequences during the operation of the MRI scanner by tapping out responses with a button box that looked like a set of piano keys, with long, rectangular buttons.
"People would see a static image shown on a video screen that detailed the sequence to be typed out," Wymbs said. "They're lying down inside the scanner and they see this image above their eyes. Interestingly, some people reported that the images looked like something out of (the video game) Guitar Hero, and, indeed, it does look a bit like guitar tablature. They would have to type out the 'notes' from left to right, as you normally would when reading music.
"After practicing a sequence for 200 trials, they would get pretty good at it," Wymbs added. "After awhile, the note patterns become familiar. At the start of the training, it would take someone about four and a half seconds to complete each sequence of 12 button presses. By the end of the experiment, the average participant could produce the same sequence in under three seconds."
The researchers' goal was to look at which areas of the brain support the two-part process of chunking. "We feel that the motor process, or the concatenation process as we refer to it in the paper, tends to take over as you continue to practice and continue to learn the sequences," Wymbs said. "That's the one that's tied to the motor output system -- the thing that's actually accomplishing what we set out to do."
With the experience of repeating a motor sequence, such as typing out a phone number, speaking, typing on a computer, or even texting, it becomes more automatic. "With automaticity comes the recruitment of core motor output regions," Wymbs said.
The scientists discovered that the putamen -- a brain region that is critically important to movement -- supports the concatenation process of motor chunking, with robust connectivity to parts of the brain that are intimately tied to the output of skilled motor behavior. On the other hand, they found that cortical regions in the left hemisphere respond more during the parsing process of motor chunking. "These regions have been linked to the manipulation of motor information, which is something that we probably do more of when we just begin to learn the sequences as chunks," Wymbs said.
"Initially, when you're doing one of these 12-element sequences, you want to pause," Wymbs added. "That would evoke more of the parsing mechanism. But then, over time, as you learn a sequence so that it becomes more automatic, and the concatenation process takes over and it wants to put all of these individual elements into a single fluid behavior."
According to Wymbs, the findings could have implications for the study and diagnosis of Parkinson's and other diseases of the motor system that involve action. "We show here that there are two potentially competing systems that lead to the isolation of different systems that both work to allow us to process things efficiently when we're learning," Wymbs said.

Fish Oil Fails to Stave Off Mental Decline

I'm sure lots of us are taking this for cholesterol reasons but it doesn't seem to help cognitively. I'll keep taking it.
Full story at the link.
http://www.medpagetoday.com/Geriatrics/Dementia/33247

Action Points

• Previous observational studies have suggested that diets high in omega-3 polyunsaturated fatty acids may protect people from cognitive decline and dementia.
• This review of randomized controlled trials found no direct evidence of omega 3 fatty acids supplementation on cognitive function in cognitively healthy older people.

‘Google for docs’ brings a new kind of smart searching to medical research

So if you ask your doctor a question and the reply is 'I don't know' OR 'All strokes are different'. Ask them to check  Google for docs.
http://medcitynews.com/2012/06/google-for-docs-brings-a-new-kind-of-smart-searching-to-medical-research/

Stroke Rehab while sleeping

I can't waste any part of the day. I now can lay on my stomach while my left arm lies by my side, due to bicep spasticity I only last 5 minutes. I then hang it over the edge of the bed. To get it back on the bed I have to roll onto my back. The left hand lays flat under the pillow while I sleep on my right side. Recently I've noticed that my left fingers sometimes go to full extension, I've no idea what triggers it or I would do it constantly

Repeated injection of PEGylated solid lipid nanoparticles induces accelerated blood clearance in mice and beagles

This sounds like a useful process for hemorrhages. So get your researcher to explain how they would set up a study for this for stroke.
http://www.dovepress.com/articles.php?article_id=10086
Abstract: Surface modification of nanocarriers with amphiphilic polymer polyethylene glycol (PEG), known as PEGylation, is regarded as a major breakthrough in the application of nanocarriers. However, PEGylated nanocarriers (including liposomes and polymeric nanoparticles) induce what is referred to as the “accelerated blood clearance (ABC) phenomenon” upon repeated injection and consequently they lose their sustained circulation characteristics. Despite this, the present authors are not aware of any reports of accelerated clearance due to repeated injection for PEGylated solid lipid nanoparticles (SLNs), another promising nanocarrier. This study investigated the pharmacokinetics of PEGylated SLNs upon repeated administration in mice; moreover, the impact of circulation time on the induction of the ABC phenomenon was studied in beagles for the first time. The ABC index, selected as the ratio of the area under the concentration-time curve from time 0 to the last measured concentration of a second injection to that of the first injection, was used to evaluate the extent of this phenomenon. Results showed that the PEGylated SLNs exhibited accelerated clearance from systemic circulation upon repeated injection, both in mice and in beagles, and the ratio for the different time intervals, which showed that the ABC index exhibited significant difference within 30 minutes following the second injection, was good enough to evaluate the magnitude of ABC. This ABC index indicated that the 10 mol% PEG SLNs with a suitable prolonged circulation time induced the most marked ABC phenomenon in this research. This study demonstrated that, like PEGylated nanocarriers such as liposomes and polymeric nanoparticles, PEGylated SLNs induced the ABC phenomenon upon repeated injection – the beagle was a valuable experimental animal for this research. Furthermore, the authors considered that a relatively extended circulation time of the initial dose may be the underlying major factor determining the induction of the ABC phenomenon.

Potential treatment could prevent brain damage after strokes

I discussed this on May 18 here:
http://oc1dean.blogspot.com/2012/05/nih-funded-research-provides-new-clues.html
http://www.expatriatehealthcare.com/News/Expatriate_Health_Insurance_News_Potential_treatment_could_prevent_brain_damage_after_strokes683
A compound is being studied by international healthcare experts at the University of Missouri (MU) and the University of Notre Dame that could potentially prevent people who have suffered from a stroke from sustaining brain damage, as well as reduce the amount of harm the incident causes.

The research, which is outlined in the journal Molecular Neurodegeneration, involves the analysis of a thiirane class of gelatinase selective inhibitors and how these function on a matrix metalloproteinase enzyme (MMP), especially a substance known as MMP-9, which is known to play a role in a number of important pathological events that occur following traumatic brain injuries or similar events.

MU School of Medicine assistant professor of pathology and anatomical sciences and corresponding author of the article Zezong Gu said the inhibitors might be combined with a tissue plasminogen activator to give people who have suffered a stroke a "longer window of time to receive emergency treatment".

He pointed out that "time is a matter of life and death" for people who have had a stroke, echoing the advice of the UK's National Health Service, which says "immediate medical attention" is needed when a person begins showing signs of this condition.

"MMPs play a role in the structure of blood vessels in the brain and are also needed in the interactions between cells during development and tissue remodelling," the researcher declared.

Mr Gu stated that without regulation, these enzymes can contribute to stroke.

He suggested that the gelatinase selective inhibitor could protect the blood vessels from MMP-9's damaging effects, while preventing damage to neurons.

In 2005, the scientist had previously played the role of lead author on a study published in the Journal of Neuroscience that had revealed MMP-9 could be a promising area that therapeutic medicines for stroke patients could target.

"We are still in the research phase for this type of compound," Mr Gu declared.