Posts tagged stroke
Articles and news from the latest research reports.
Astrocyte Signaling Sheds Light on Stroke Research
New research published in The Journal of Neuroscience suggests that modifying signals sent by astrocytes, our star-shaped brain cells, may help to limit the spread of damage after an ischemic brain stroke. The study in mice, by neuroscientists at Tufts University School of Medicine, determined that astrocytes play a critical role in the spread of damage following stroke.
The National Heart Foundation reports that ischemic strokes account for 87% of strokes in the United States. Ischemic strokes are caused by a blood clot that forms and travels to the brain, preventing the flow of blood and oxygen.
Even when blood and oxygen flow is restored, however, neurotransmitter processes in the brain continue to overcompensate for the lack of oxygen, causing brain cells to be damaged. The damage to brain cells often leads to health complications including visual impairment, memory loss, clumsiness, moodiness, and partial or total paralysis.
Research and drug trials have focused primarily on therapies affecting neurons to limit brain cell damage. Phil Haydon’s group at Tufts University School of Medicine have focused on astrocytes, a lesser known type of brain cell, as an alternative path to understanding and treating diseases affecting brain cells.
In animal models, his research team has shown that astrocytes—which outnumber neurons by ten to one—send signals to neurons that can spread the damage caused by strokes. The current study determines that decreasing astrocyte signals limits damage caused by stroke by regulating the neurotransmitter pathways after an ischemic stroke.
The research team compared two sets of mice: a control group with normal astrocyte signaling levels and a group whose signaling was weakened enough to be made protective rather than destructive. To assess the effect of astrocyte protection after ischemic strokes, motor skills, involving tasks such as walking and picking up food, were tested. In addition, tissue samples were taken from both groups and compared.
“Mice with altered astrocyte signaling had limited damage after the stroke,” said first author Dustin Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at Tufts University School of Medicine. “Manipulating the astrocyte signaling demonstrates that astrocytes are critical to understanding the spread of damage following stroke.”
“Looking into ways to utilize and enhance the astrocyte’s protective properties in order to limit damage is a promising avenue in stroke research,” said senior author Phillip Haydon, Ph.D. Haydon is the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts University School of Medicine and a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
(Source: now.tufts.edu)
Gets stroke patients back on their feet
A robot is now being built to help stroke patients with training, motivation and walking.
In Europe, strokes are the most common cause of physical disability among the elderly. This often result in paralysis of one side of the body, and many patients suffer much reduced physical mobility and are often unable to walk on their own. These are the hard facts the EU project CORBYS has taken seriously. Researchers in six countries are currently developing a robotic system designed to help stroke patients re-train their bodies. The concept is based on helping the patient by constructing a system consisting of powered orthosis to help patient in moving his/her legs and a mobile platform providing patient mobility.
The CORBYS researchers are also working with the cognitive aspects. The aim is to enable the robot to interpret data from the patient and adapt the training programme to his or her capabilities and intention. This will bring rehabilitation robots to the next level.
Back to walking normally
It is vital to get stroke patients up on their feet as soon as possible. They must have frequent training exercises, and re-learn how to walk so that they can function as good as possible on their own.
Why a robot? “Absolutely, because it is difficult to meet these requirements using today’s work-intensive manual method where two therapists assisting the patient by lifting one leg after the other”, says ICT researcher Anders Liverud at SINTEF, which is one of the CORBYS project partners.
Robot-patient learning
CORBYS involves the use of physiological data such as heart rate, temperature and muscle activity measurements to provide feedback to the therapist and help control the robot. Do the patient’s legs always go where the patient want? Is the patient getting tired and stressed?
“The walking robot has several settings, and the therapist selects the correct mode based on how far the patient has come in his or her rehabilitation”, says Liverud. “The first step is to attach sensors to the patient’s body and let them walk on a treadmill. A therapist manually corrects the walking pattern and, with the help of the sensors, create a model of the patient’s walking pattern”, he says.
In the next mode, the system adjusts the walking pattern to the defined model. New adjustments are made and are used to improve optimisation of the walking pattern.
“The patient wears an EEG cap which measures brain activity”, says Liverud. “By using these signals combined with input from other physiological and system sensors, the robotic system registers whether the patient wants to stop, change speed or turn, and can adapt immediately”, he says. “The robot continues to correct any walking pattern errors. However, since it also allows the patient the freedom to decide where and how he or she walks, the patient experiences control and keeps motivation to continue with the training”, says Liverud.
Working with Europe
The European researchers have now completed specification of the system and its components, and construction of the robot is underway.
Construction involves a large team. The University of Bremen is heading the project and developing the architecture to integrate all system modules, and German wheelchair, orthosis and robotics experts are constructing the mechanical components, while two UK universities are working with cognitive aspects. Spanish specialists are addressing brain activity measurements and the University of Brussels is looking into robot control. SINTEF is working with the sensors and the final functional integration of the system. In a year’s time construction will be completed and the robot will be tested on stroke patients at rehabilitation institutes in Slovenia and Germany. The CORBYS project has a total budget of EUR 8.7 million.
Is it a Stroke or Benign Dizziness? A Simple Bedside Test Can Tell
A bedside electronic device that measures eye movements can successfully determine whether the cause of severe, continuous, disabling dizziness is a stroke or something benign, according to results of a small study led by Johns Hopkins Medicine researchers.
"Using this device can directly predict who has had a stroke and who has not," says David Newman-Toker, M.D., Ph.D., an associate professor of neurology and otolaryngology at the Johns Hopkins University School of Medicine and leader of the study described in the journal Stroke. “We’re spending hundreds of millions of dollars a year on expensive stroke work-ups that are unnecessary, and probably missing the chance to save tens of thousands of lives because we aren’t properly diagnosing their dizziness or vertigo as stroke symptoms.”
Newman-Toker says if additional larger studies confirm these results, the device could one day be the equivalent of an electrocardiogram (EKG), a simple noninvasive test routinely used to rule out heart attack in patients with chest pain. And, he adds, universal use of the device could “virtually eliminate deaths from misdiagnosis and save a lot of time and money.”
To distinguish stroke from a more benign condition, such as vertigo linked to an inner ear disturbance, specialists typically use three eye movement tests that are essentially a stress test for the balance system. In the hands of specialists, these bedside clinical tests (without the device) have been shown in several large research studies to be extremely accurate — “nearly perfect, and even better than immediate MRI,” says Newman-Toker. One of those tests, known as the horizontal head impulse test, is the best predictor of stroke. To perform it, doctors or technicians ask patients to look at a target on the wall and keep their eyes on the target as doctors move the patients’ heads from side to side. But, says Newman-Toker, it requires expertise to determine whether a patient is making the fast corrective eye adjustments that would indicate a benign form of dizziness as opposed to a stroke.
For the new study, researchers instead performed the same test using a small, portable device — a video-oculography machine that detects minute eye movements that are difficult for most physicians to notice. The machine includes a set of goggles, akin to swimming goggles, with a USB-connected webcam and an accelerometer in the frame. The webcam is hooked up to a laptop where a continuous picture of the eye is taken. Software interprets eye position based on movements and views of the pupil, while the accelerometer measures the speed of the movement of the head.
Newman-Toker says the test could be easily employed to prevent misdiagnosis of as many as 100,000 strokes a year, leading to earlier stroke diagnosis and more efficient triage and treatment decisions for patients with disabling dizziness. Overlooked strokes mean delayed or missed treatments that lead to roughly 20,000 to 30,000 preventable deaths or disabilities a year, he says. The technology, he adds, could someday be used in a smartphone application to enable wider access to a quick and accurate diagnosis of strokes whose main symptom is dizziness, as opposed to one-sided weakness or garbled speech.
The diagnosis of stroke in patients with severe dizziness, vomiting, difficulty walking and intolerance to head motion is difficult, Newman-Toker says. He estimates there are 4 million emergency department visits annually in the United States for dizziness or vertigo, at least half a million of which involve patients at high risk for stroke. The most common causes are benign inner ear conditions, but many emergency room doctors, Newman-Toker says, find it nearly impossible to tell the difference between the benign conditions and something more serious, such as a stroke. So they often rely on brain imaging - usually a CT scan, an expensive and inaccurate technology for this particular diagnosis.
The Hopkins-led study enrolled 12 patients at The Johns Hopkins Hospital and the University of Illinois College of Medicine at Peoria, who later underwent confirmatory MRI. Six were diagnosed with stroke and six with a benign condition using video-oculography. MRI later confirmed all 12 diagnoses.
New FDA-Approved Clot Removal Devices Show Promise for Treating Stroke Patients
Specialists at Stony Brook Medicine’s Cerebrovascular and Stroke Center (CVC) are treating patients with a new generation of blood clot removal devices that show promise in successfully revascularizing stroke patients, including those with large vessel blockages. The Solitaire Flow Restoration Device and the Trevo device, approved by Food and Drug Administration (FDA) in 2012 to treat stroke caused by the sudden obstruction of a brain blood vessel (acute ischemic stroke) showed improved results over a previous standard and first generation clot-removal device in clinical trials.
“We have had excellent outcomes using these new devices,” said David Fiorella, M.D., Ph.D., a Professor of Clinical Neurological Surgery and Radiology at Stony Brook University School of Medicine and Co-Director of the CVC. “In acute ischemic stroke, ‘time is brain,’ and in some cases just minutes matter. Therefore, restoring blood flow in an effective and timely manner is critical to the survival and recovery of stroke patients. These new devices enable us to quickly restore blood flow and retrieve the clot in most patients,” said Dr. Fiorella, who has performed some 30 procedures on stroke patients using the new devices.
“These blot clot removal devices are an important new component of our armamentarium against stroke” said Henry Woo, MD, Professor of Neurological Surgery and Radiology and Co-Director of the CVC, who has also used both devices in patient procedures. “Our center provides endovascular treatment for acute stroke 24/7, and by having the latest technologies to remove brain blood clots, and the expertise to perform endovascular procedures, our Center remains on the cutting-edge against this life-threatening condition.”
Recent results of clinical trials reported in The New England Journal of Medicine (February 2013) about the use of first generation of blood clot removal devices in the endovascular treatment of acute ischemic stroke revealed that endovascular treatment does not result in better patient outcomes compared to standard drug treatments. Dr. Fiorella contends that while these trial results are important in the search for the best treatment protocols for acute ischemic stroke, the new devices and techniques are markedly better than those used to treat the majority of patients in these trials and may yet prove to be the most effective approach in select patients. Further research trials are being conducted at Stony Brook to investigate the efficacy of these newer, better devices in acute ischemic stroke.
The new devices that Stony Brook cerebrovascular specialists use to perform revascularization are expandable wire-mesh systems that collapse and are delivered into the brain blood vessels through small flexible tubes (microcatheters) which are guided from the groin to the brain. The devices open at the site of the clot, displacing the occlusion and immediately restoring blood flow to the brain. When the devices are withdrawn from the blood vessel, they take the clot with them, allowing the clot to be removed from the blood vessel.
Ability of brain to protect itself from damage revealed
(Image: Matthias Kulka / Corbis)
The origin of an innate ability the brain has to protect itself from damage that occurs in stroke has been explained for the first time.
The Oxford University researchers hope that harnessing this inbuilt biological mechanism, identified in rats, could help in treating stroke and preventing other neurodegenerative diseases in the future.
'We have shown for the first time that the brain has mechanisms that it can use to protect itself and keep brain cells alive,' says Professor Alastair Buchan, Head of the Medical Sciences Division and Dean of the Medical School at Oxford University, who led the work.
The researchers report their findings in the journal Nature Medicine and were funded by the UK Medical Research Council and National Institute for Health Research.
Stroke is the third most common cause of death in the UK. Every year around 150,000 people in the UK have a stroke.
It occurs when the blood supply to part of the brain is cut off. When this happens, brain cells are deprived of the oxygen and nutrients they need to function properly, and they begin to die.
'Time is brain, and the clock has started immediately after the onset of a stroke. Cells will start to die somewhere from minutes to at most 1 or 2 hours after the stroke,' says Professor Buchan.
This explains why treatment for stroke is so dependent on speed. The faster someone can reach hospital, be scanned and have drugs administered to dissolve any blood clot and get the blood flow re-started, the less damage to brain cells there will be.
It has also motivated a so-far unsuccessful search for ‘neuroprotectants’: drugs that can buy time and help the brain cells, or neurons, cope with damage and recover afterwards.
The Oxford University research group have now identified the first example of the brain having its own built-in form of neuroprotection, so-called ‘endogenous neuroprotection’.
They did this by going back to an observation first made over 85 years ago. It has been known since 1926 that neurons in one area of the hippocampus, the part of the brain that controls memory, are able to survive being starved of oxygen, while others in a different area of the hippocampus die. But what protected that one set of cells from damage had remained a puzzle until now.
'Previous studies have focused on understanding how cells die after being depleted of oxygen and glucose. We considered a more direct approach by investigating the endogenous mechanisms that have evolved to make these cells in the hippocampus resistant,' explains first author Dr Michalis Papadakis, Scientific Director of the Laboratory of Cerebral Ischaemia at Oxford University.
Working in rats, the researchers found that production of a specific protein called hamartin allowed the cells to survive being starved of oxygen and glucose, as would happen after a stroke.
They showed that the neurons die in the other part of the hippocampus because of a lack of the hamartin response.
The team was then able to show that stimulating production of hamartin offered greater protection for the neurons.
Professor Buchan says: ‘This is causally related to cell survival. If we block hamartin, the neurons die when blood flow is stopped. If we put hamartin back, the cells survive once more.’
Finally, the researchers were able to identify the biological pathway through which hamartin acts to enable the nerve cells to cope with damage when starved of energy and oxygen.
The group points out that knowing the natural biological mechanism that leads to neuroprotection opens up the possibility of developing drugs that mimic hamartin’s effect.
Professor Buchan says: ‘There is a great deal of work ahead if this is to be translated into the clinic, but we now have a neuroprotective strategy for the first time. Our next steps will be to see if we can find small molecule drug candidates that mimic what hamartin does and keep brain cells alive.
'While we are focussing on stroke, neuroprotective drugs may also be of interest in other conditions that see early death of brain cells including Alzheimer's and motor neurone disease,' he suggests.
(Source: eurekalert.org)
Omega-3 Lipid Emulsions Markedly Protect Brain After Stroke in Mouse Study
Triglyceride lipid emulsions rich in an omega-3 fatty acid injected within a few hours of an ischemic stroke can decrease the amount of damaged brain tissue by 50 percent or more in mice, reports a new study by researchers at Columbia University Medical Center.
The results suggest that the emulsions may be able to reduce some of the long-term neurological and behavioral problems seen in human survivors of neonatal stroke and possibly of adult stroke, as well. The findings were published today in the journal PLoS One.
Currently, clot-busting tPA (recombinant tissue-type plasminogen activator) is the only treatment shown to improve recovery from ischemic stroke. If administered soon after stroke onset, the drug can restore blood flow to the brain but may not prevent injured, but potentially salvageable, neurons from dying.
Drugs with neuroprotective qualities that can prevent the death of brain cells damaged by stroke are needed, but even after 30 years of research and more than 1000 agents tested in animals, no neuroprotectant has been found effective in people.
Omega-3 fatty acids may have more potential as neuroprotectants because they affect multiple biochemical processes in the brain that are disturbed by stroke, said the study’s senior author, Richard Deckelbaum, MD, director of the Institute of Human Nutrition at Columbia’s College of Physicians & Surgeons. “The findings also may be applicable to other causes of ischemic brain injury in newborns and adults,” added co-investigator Vadim S. Ten, MD, PhD, an associate professor of pediatrics from the Department of Pediatrics at Columbia.
The effects of the omega-3 fatty acids include increasing the production of natural neuroprotectants in the brain, reducing inflammation and cell death, and activating genes that may protect brain cells. Omega-3 fatty acids also markedly reduce the release of harmful oxidants into the brain after stroke. “In most clinical trials in the past, the compounds tested affected only one pathway. Omega-3 fatty acids, in contrast, are very bioactive molecules that target multiple mechanisms involved in brain death after stroke,” Dr. Deckelbaum said.
The study revealed that an emulsion containing only DHA (docosahexaenoic acid), but not EPA (eicosapentaenoic acid), in a triglyceride molecule reduced the area of dead brain tissue by about 50 percent or more even when administered up to two hours after the stroke. Dr. Deckelbaum noted, “Since mice have a much faster metabolism than humans, longer windows of time for therapeutic effect after stroke are likely in humans.” Eight weeks after the stroke, much of the “saved” mouse brain tissue was still healthy, and no toxic effects were detected.
(Image: Shutterstock)
Teaching the brain to speak again
Cynthia Thompson, a world-renowned researcher on stroke and brain damage, will discuss her groundbreaking research on aphasia and the neurolinguistic systems it affects Feb. 16 at the annual meeting of the American Association for the Advancement of Science (AAAS). An estimated one million Americans suffer from aphasia, affecting their ability to understand and/or produce spoken and/or written language.
For three decades, Thompson has played a crucial role in demonstrating the brain’s plasticity, or ability to change. “Not long ago, the conventional wisdom was that people only could recover language within three months to a year after the onset of stroke,” she says. “Today we know that, with appropriate training, patients can make gains as much as 10 years or more after a stroke.”
Thompson has probably contributed more findings on the effects of brain damage on language processing and the ways the brain and language recover from stroke than any other single researcher. Her particular interest is agrammatic aphasia, which impairs abstract knowledge of grammatical sentence structure and makes sentence production and understanding difficult.
Among the first researchers to use functional magnetic resonance imaging to study recovery from stroke, Thompson found that behavior treatment that focused on improving impaired language processing affects not only the ability to understand and produce language but also brain activity.
She found shifts in neural activity in both cerebral hemispheres associated with recovery, with the greatest recovery seen in undamaged brain regions within the language network engaged by healthy people, albeit regions recruited for various language activities.
"It’s a matter of ‘use it or lose it,’" Thompson says. "The brain has the capacity to learn and relearn throughout life, and it is directly affected by the activities we engage in. Language training that focuses on principles of normal language processing stimulates the recovery of neural networks that support language."
Thompson will discuss research she will conduct as principal investigator of a $12 million National Institutes of Health Clinical Research Center award to study biomarkers of recovery in aphasia.
Working with investigators from a number of universities, Thompson will explore the role blood flow plays in language recovery in chronic stroke patients. In addition, she will conduct cutting-edge, exploratory research using eye tracking to understand how people compute language as they hear it in real time. Eye-tracking techniques have been found to discern subtle problems underlying language deficits in acquired aphasia.
In a landmark 2010 study, she and colleagues discovered two critical variables related to understanding brain damage recovery. They found that stroke not only results in cell death in certain regions of the brain but that it also decreases blood flow (perfusion) to living cells that are adjacent (and sometimes even distant) to the lesion.
Until that study, hypoperfusion (diminished blood flow) was thought only to be associated with acute stroke. Her team also found that greater hypoperfusion led to poorer recovery.
(Source: eurekalert.org)
‘Robot’ cells answer call to arms
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.”
Stroke Damage in Mice Overcome by Training that ‘Rewires’ Brain Centers
Johns Hopkins researchers have found that mice can recover from physically debilitating strokes that damage the primary motor cortex, the region of the brain that controls most movement in the body, if the rodents are quickly subjected to physical conditioning that rapidly “rewires” a different part of the brain to take over lost function.
Their research, featuring precise, intense and early treatment, and tantalizing clues to the role of a specific brain area in stroke recovery, is described online in the journal Stroke.
"Despite all of our approved therapies, stroke patients still have a high likelihood of ending up with deficits," says study leader Steven R. Zeiler, M.D., Ph.D., an assistant professor of neurology at the Johns Hopkins University School of Medicine. "This research allows us the opportunity to test meaningful training and pharmacological ways to encourage recovery of function, and should impact the care of patients."
With improved acute care for stroke, more patients are surviving. Still, as many as 60 percent are left with diminished use of an arm or leg, and one-third need placement in a long-term care facility. The economic cost of disability translates to more than $30 billion in annual care.
New stroke gene discovery could lead to tailored treatments
A study led by King’s College London has identified a new genetic variant associated with stroke. By exploring the genetic variants linked with blood clotting – a process that can lead to a stroke – scientists have discovered a gene which is associated with large vessel and cardioembolic stroke but has no connection to small vessel stroke.
Published in the journal Annals of Neurology, the study provides a potential new target for treatment and highlights genetic differences between different types of stroke, demonstrating the need for tailored treatments.
Approximately 152,000 people in Britain have a stroke each year, costing the UK over £8.2 billion. While there are thought to be 1.2 million stroke survivors in the UK, more than half have been left with disabilities that affect their daily lives.
A stroke occurs when the blood supply to the brain is cut off, often due to a blood clot blocking an artery that carries blood to the brain, which then leads to brain cell damage. Coagulation (blood clotting) abnormalities, particularly easy clotting of the blood, are therefore common contributing factors in the development of stroke.
Dr Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s and lead author of the paper, said: ‘Previous studies have demonstrated the influence of genetic factors on the components of coagulation. The goal of this study was to extend these observations to determine if they were further associated with different types of stroke.’
The research was carried out in three stages. The first consisted of a genome-wide association study (GWAS) in 2100 healthy volunteers which identified 23 independent genetic variants that were involved in coagulation. The second stage examined the 23 variants in 4200 stroke and non-stroke cases from centres across Europe (Wellcome Trust Case Control Consortium 2 and MORGAM collections) and found that a particular mutation on the ABO gene was significantly associated with stroke.
Stage three of the study used the MetaStroke cohort, a project of the International Stroke Genetics Consortium which comprises 8900 stroke cases recruited from centres in the Europe, USA and Australia, whose DNA has been collected and undergone GWA scan. It was confirmed that a variant in the ABO blood type gene was associated with stroke, a finding specific to large vessel and cardioembolic stroke.
Dr Williams said: ‘The discovery of the association between this genetic variant and stroke identifies a new target for potential treatments, which could help to reduce the risk of stroke in the future. It is also significant that no association was found with small vessel disease, as this suggests that stroke subtypes involve different genetic mechanisms which emphasises the need for individualised treatment.’