Posts tagged stroke
Articles and news from the latest research reports.
Faster help for stroke victims
Scientists have developed a quick, easy and cheap vision test to find out which part – and how much – of the brain of a stroke victim has been damaged, potentially enabling them to save more lives.
The test requires patients to look into a device for about ten minutes, enabling it to be used in the early stages of a stroke – even if the patient cannot move their limbs or speak.
This can help doctors diagnose and treat the stroke quickly and accurately, which is vital, as early treatment can greatly improve a person’s chances of survival and recovery, say Dr Corinne Carle and Professor Ted Maddess from The Vision Centre and The Australian National University.
According to the World Health Organisation, stroke is currently the world’s sixth commonest cause of death, accounting for 4.9% of all fatalities. In Australia it kills about 9000 people a year and hospitalises 35,000.
“Our new test automatically tracks the response of the patient’s eye pupils to different colours, and can show doctors whether the injury is located in the evolutionarily ‘new brain’ or the ‘old brain’,” Dr Carle says.
“The distinction is important because the ‘old brain’, or midbrain, controls things like the heart rate and blood pressure of the body. So if you find that the midbrain has been damaged, you’ll need to treat the patient much more aggressively, because there’s a higher risk of death.”
On the other hand, an injury in the ‘new brain’ – the cortex – may cause permanent blindness in a part of the person’s visual field, or difficulty in their thoughts, speech and movement, but has a lower risk of death, she says.
Using the TrueField Analyzer, a device developed by Prof. Maddess’ Vision Centre team and the Australian company Seeing Machines, the researchers tested how the pupils respond to images on LCD screens. A mixture of red, green and yellow coloured stimuli were provided to each eye, at 24 locations in the person’s visual field.
Two video cameras using infrared lighting recorded the instant response of the pupils, which was then analysed by a computer.
The colours red, green and yellow were chosen because they are processed by different parts of the brain, Dr Carle explains. In mammals, the cortex, or ‘new brain’, is the most recently evolved area, and allows humans to differentiate between red and green.
The ‘ancient’ midbrain, on the other hand, is red-green colourblind, but can detect the colour yellow.
“If the pupils don’t react when red changes to green, we know that the damage is in the cortex. The same concept applies to the yellow stimulus,” says Dr Carle. “The test has been successful in checking the vision of people with glaucoma or type-1 diabetes, and we have now tweaked the stimuli for stroke patients as well.”
Prof. Ted Maddess says that the test will complement various types of brain scans.
“A CT scan tells you where the bleed is, but it doesn’t show you everything,” he says. “For instance, the blood could have cleared up in a particular part of the brain during the scan, or where swelling has reduced the function of a nearby part that looks fine on the scan. It may also miss injuries that are too small, or those that occur in the midbrain, where it doesn’t scan well.”
This is where the test can be useful, Prof. Maddess says. As every single vision cell is wired into a different part of the brain, by testing a particular area in the visual field, doctors can check if the corresponding part of the brain is functioning or not.
The test can be used to monitor stroke patients’ recovery, Prof. Maddess says: “Currently, apart from brain scans, there is no cheap, routine test that can quantify the amount of improvement that results from a treatment. Stroke patients have a very high risk of recurrence, so it’s important that doctors can accurately assess their recovery.”
“The TrueField Analyzer is small, affordable and the test only takes ten minutes,” he says. Working together with neurologists, the research team will start clinical tests with stroke patients in February this year.
The team’s study “The pupillary response to color and luminance variant multifocal stimuli” by Corinne F. Carle, Andrew C. James and Ted Maddess is published in the latest issue of Investigative Ophthalmology & Visual Science (IOVS).
(Source: scinews.com.au)
Research offers new targets for stroke treatments
New research from the University of Georgia identifies the mechanisms responsible for regenerating blood vessels in the brain.
Looking for ways to improve outcomes for stroke patients, researchers led by the UGA College of Pharmacy assistant dean for clinical programs Susan Fagan used candesartan, a commonly prescribed medication for lowering blood pressure, to identify specific growth factors in the brain responsible for recovery after a stroke.
The results were published online Dec. 4 in the Journal of Pharmacology and Experimental Therapeutics
Although candesartan has been shown to protect the brain after a stroke, its use is generally avoided because lowering a person’s blood pressure quickly after a stroke can cause problems-like decreasing much-needed oxygen to the brain-during the critical period of time following a stroke.
"The really unique thing we found is that candesartan can increase the secretion of brain derived neurotrophic factor, and the effect is separate from the blood pressure lowering effect," said study coauthor Ahmed Alhusban, who is a doctoral candidate in the College of Pharmacy. "This will support a new area for treatments of stroke and other brain injury."
Alhusban and Fagan worked with Anna Kozak, a research scientist in the college, and Adviye Ergul, a professor and director of the physiology graduate program at Georgia Health Sciences University. They are the first to show that the positive effects of candesartan on brain blood vessel growth are caused by brain derived neurotrophic factor, or BDNF.
The research shows that when candesartan blocks the angiotensin II type 1 receptor, which lowers blood pressure, it stimulates the AT2 receptor and increases the secretion of BDNF, which encourages brain repair through the growth of new blood vessels.
"BDNF is a key player in learning and memory," said Fagan, the Albert W. Jowdy Professor. "A reduction of BDNF in the brain has been associated with Alzheimer’s disease and depression, so increasing this growth factor with a common medication is exciting."
AT2 is a brain receptor responsible for angiogenesis, or the growth of new blood vessels from pre-existing vessels. Angiogenesis is a normal and vital process in human growth and development-as well as in healing.
(Image: iStock)
Silent stroke can cause Parkinson’s disease
Scientists at The University of Manchester have for the first time identified why a patient who appears outwardly healthy may develop Parkinson’s disease.
Whilst conditions such as a severe stroke have been linked to the disease, for many sufferers the tremors and other symptoms of Parkinson’s disease can appear to come out of the blue. Researchers at the university’s Faculty of Life Sciences have now discovered that a small stroke, also known as a silent stroke, can cause Parkinson’s disease. Their findings have been published in the journal “Brain Behaviour and Immunity”.
Unlike a severe stroke, a silent stroke can show no outward symptoms of having taken place. It happens when a blood vessel in the brain is blocked for only a very short amount of time and often a patient won’t know they have suffered from one. However, it now appears one of the lasting effects of a silent stroke can be the death of dopaminergic neurons in the substantia nigra in the brain, which is an important region for movement coordination.
Dr. Emmanuel Pinteaux led the research: “At the moment we don’t know why dopaminergic neurons start to die in the brain and therefore why people get Parkinson’s disease. There have been suggestions that oxidative stress and aging are responsible. What we wanted to do in our study was to look at what happens in the brain away from the immediate area where a silent stroke has occurred and whether that could lead to damage that might result in Parkinson’s disease.”
The team induced a mild stroke similar to a silent stroke in the striatum area of the brain in mice. They found there was inflammation and brain damage in the striatum following the stroke, which they had expected. What the researchers didn’t expect was the impact on another area of the brain, the substantia nigra. When they analysed the substantia nigra they recorded a rapid loss of Substance P (a key chemical involved in its functions) as well as inflammation.
The team then analysed changes in the brain six days after the mild stroke and found neurodegeneration in the substantia nigra. Dopaminergic neurones had been killed.
Talking about the findings Dr Pinteaux said: “It is well known that inflammation following a stroke can be very damaging to the brain. But what we didn’t fully appreciate was the impact on areas of the brain away from the location of the stroke. Our work identifying that a silent stroke can lead to Parkinson’s disease shows it is more important than ever to ensure stroke patients have swift access to anti-inflammatory medication. These drugs could potentially either delay or stop the on-set of Parkinson’s disease.”
Dr Pinteaux continued: “What our findings also point to is the importance of maintaining a healthy lifestyle. There are already guidelines about exercise and healthy eating to help reduce the risk of having a stroke and our research suggests that a healthy lifestyle can be applied to Parkinson’s disease as well.”
Following the publication of these findings, Dr Pinteaux hopes to set up a clinical investigation on people who have had a silent stroke to assess dopaminergic neuron degeneration. In the meantime he will be working closely will colleagues at The University of Manchester to better understand the mechanisms of inflammation in the substantia nigra.
Even the Smallest Possible Stroke Can Damage Brain Tissue and Impair Cognitive Function
Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to miniscule blood vessels that feed brain cells. The team reports their results in the December 16 advance online edition of Nature Neuroscience.
"The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernable impact on the behavior of a rat," said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.
Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.
These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.
"It’s controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve," said David Kleinfeld, professor of physics and neurobiology, who leads the research group.
To see whether such minute damage could change behavior, the scientists trained thirsty rats to leap from one platform to another in the dark to get water.
The rats readily jump if they can reach the second platform with a paw or their snout, or stretch farther to touch it with their whiskers. Many rats can be trained to rely on a single whisker if the others are clipped, but if they can’t feel the far platform, they won’t budge.
"The whiskers line up in rows and each one is linked to a specific spot in the brain," Shih said. "By training them to use just one whisker, we were able to distill a behavior down to a very small part of the brain."
When Shih blocked single microvessels feeding a column of brain cells that respond to signals from the remaining whisker, the rats still crossed to the far platform when the gap was small. But when it widened beyond the reach of their snouts, they quit.
The FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer’s disease, ameliorated these effects. Rats that received the drug jumped whisker-wide gaps, and their brains showed fewer signs of damage.
"This data shows us, for the first time, that even a tiny stroke can lead to disability," said Patrick D. Lyden, a co-author of the study and chair of the department of neurology at Cedars-Sinai Medical Center in Los Angeles. "I am afraid that tiny strokes in our patients contribute—over the long term—to illness such as dementia and Alzheimer’s disease," he said, adding that "better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."
“We used powerful tools from biological physics, many developed in Kleinfeld’s laboratory at UC San Diego, to link stroke to dementia on the unprecedented small scale of single vessels and cells,” Shih said. “At my new position at MUSC, I plan to work on ways to improve the detection of micro-lesions in human patients with MRI. This way clinicians may be able to diagnose and treat dementia earlier.”
A blood clot is one of the final steps in a complex process with which the human body seals a rupture in an injured blood vessel. Clotting involves interactions between millions of blood cells, microscopic cell fragments called platelets, and various proteins. First, platelets rush to the site of injury and join together with an inner layer of fibrin and collagen proteins to form a sticky web around the break. Red blood cells are then trapped in the web, forming a clot. In certain cases a clot can block arteries and vessels that feed the brain or heart, impeding blood flow and eventually contributing to a stroke or heart attack.
Creating accurate, real-time computer simulations of how blood clots work—and the role they play in medical emergencies—could, in the future, dramatically improve the way that doctors predict the risk of damaging clots and treat the damage incurred by strokes and heart attacks. The models could, for example, help doctors position a stent—a tube placed in a blood vessel to help keep it open—before a risky surgery or offer a new way to test the effects of drugs on the circulatory system. In order to be truly accurate and useful, however, such simulations would have to account for billions of tiny cellular machines, all moving through the blood—something that has never been comprehensively modeled before.
Study Details Brain Damage Triggered by Mini-Strokes
A new study appearing today in the Journal of Neuroscience details for the first time how “mini-strokes” cause prolonged periods of brain damage and result in cognitive impairment. These strokes, which are often imperceptible, are common in older adults and are believed to contribute to dementia.
“Our research indicates that neurons are being lost as a result of delayed processes following a mini-strokes that may differ fundamentally from those of acute ischemic events,” said Maiken Nedergaard, M.D., D.M.Sc., the lead author of the study and professor of Neurosurgery at the University of Rochester Medical Center (URMC). “This observation suggests that the therapeutic window to protect cells after these tiny strokes may extend to days and weeks after the initial injury.”
The prevalence of mini-strokes, or microinfarcts, has only been recently appreciated because common imaging techniques, such as MRI, are typically not sensitive enough to detect these microscopic injuries.
Similar to severe ischemic strokes, mini-strokes are caused when blood flow is blocked to a small area of the brain, usually by particle that travelled there from another part of the body. But unlike acute ischemic strokes – which bring about immediate symptoms such as numbness, blurry vision, and slurred speech – mini-strokes usually pass without notice. However, it is increasingly appreciated that these smaller strokes have a lasting impact on neurological function.
Microinfarcts are far more common than previously understood; it is believed that about 50 percent of individuals over the age of 60 have experienced at least one mini-stroke. Studies have also correlated the presence of mini-strokes with the symptoms of dementia. An estimated 55 percent of individuals with mild dementia and upwards of 70 percent of individuals with more severe symptoms show evidence of past mini-strokes. This association has led researchers to believe that these mini-strokes may be key contributors to age-related cognitive decline and dementia.
Nedergaard and her colleagues were the first to develop an animal model in which the complex progression and, ultimately, the cognitive impact of mini-strokes could be observed. Her team found that, in most instances, these strokes result in a prolonged period of damage to the brain.
Changes in the gut bacteria protect against stroke
The human body contains ten times more bacterial cells than human cells, most of which are found in the gut. These bacteria contain an enormous number of genes in addition to our host genome, and are collectively known as the gut metagenome.
How does the metagenome affect our health? This question is currently being addressed by researchers in the rapidly expanding field of metagenomic research. Several diseases have been linked to variations in the metagenome. Researchers at Chalmers University of Technology and Gothenburg University now also show that changes in the gut metagenome can be linked to atherosclerosis and stroke.
The researchers compared a group of stroke patients with a group of healthy subjects and found major differences in their gut microbiota. In particular, they showed that genes required for the production of carotenoids were more frequently found in gut microbiota from healthy subjects. The healthy subjects also had significantly higher levels of a certain carotenoid in the blood than the stroke survivors.
Carotenoids are a type of antioxidant, and it has been claimed for many years that they protect against angina and stroke. Thus, the increased incidence of carotenoid-producing bacteria in the gut of healthy subjects may offer clues to explain how the gut metagenome affects disease states.
Carotenoids are marketed today as a dietary supplement. The market for them is huge, but clinical studies of their efficacy in protecting against angina and stroke have produced varying results. Jens Nielsen, Professor of Systems Biology at Chalmers, says that it may be preferable to take probiotics instead – for example dietary supplements containing types of bacteria that produce carotenoids.
“Our results indicate that long-term exposure to carotenoids, through production by the bacteria in the digestive system, has important health benefits. These results should make it possible to develop new probiotics. We think that the bacterial species in the probiotics would establish themselves as a permanent culture in the gut and have a long-term effect”.
“By examining the patient’s bacterial microbiota, we should also be able to develop risk prognoses for cardiovascular disease”, says Fredrik Bäckhed, Professor of Molecular Medicine at Gothenburg University. ”It should be possible to provide completely new disease-prevention options”.
Double Duty: Immune System Regulator Found to Protect Brain from Effects of Stroke
A small molecule known to regulate white blood cells has a surprising second role in protecting brain cells from the deleterious effects of stroke, Johns Hopkins researchers report. The molecule, microRNA-223, affects how cells respond to the temporary loss of blood supply brought on by stroke — and thus the cells’ likelihood of suffering permanent damage.
“We set out to find a small molecule with very specific effects in the brain, one that could be the target of a future stroke treatment,” says Valina Dawson, Ph.D., a professor in the Johns Hopkins University School of Medicine’s Institute for Cell Engineering. “What we found is this molecule involved in immune response, which also acts in complex ways on the brain. This opens up a suite of interesting questions about what microRNA-223 is doing and how, but it also presents a challenge to any therapeutic application.” A report on the discovery is published in the Nov. 13 issue of the Proceedings of the National Academy of Sciences.
RNA is best known as a go-between that shuttles genetic information from DNA and then helps produce proteins based on that information. But, Dawson explains, a decade ago researchers unearthed a completely different class of RNA: small, nimble fragments that regulate protein production. In the case of microRNA, one member of this class, that control comes from the ability to bind to RNA messenger molecules carrying genetic information, and thus prevent them from delivering their messages. “Compared with most ways of shutting genes off, this one is very quick,” Dawson notes.
Reasoning that this quick action, along with other properties, could make microRNAs a good target for therapy development, Dawson and her team searched for microRNAs that regulate brain cells’ response to oxygen deprivation.
To do that, they looked for proteins that increased in number in cells subjected to stress, and then examined how production of these proteins was regulated. For many of them, microRNA-223 played a role, Dawson says.
In most cases, the proteins regulated by microRNA-223 turned out to be involved in detecting and responding to glutamate, a common chemical signal brain cells use to communicate with each other. A stroke or other injury can lead to a dangerous excess of glutamate in the brain, as can a range of diseases, including autism and Alzheimer’s.
Because microRNA-223 is involved in regulating so many different proteins, and because it affects glutamate receptors, which themselves are involved in many different processes, the molecule’s reach turned out to be much broader than expected, says Maged M. Harraz, Ph.D., a research associate at Hopkins who led the study. “Before this experiment, we didn’t appreciate that a single microRNA could regulate so many proteins,” he explains.
This finding suggests that microRNA-223 is unlikely to become a therapeutic target in the near future unless researchers figure out how to avoid unwanted side effects, Dawson says.
(Source: hopkinsmedicine.org)
Results: At the moment that someone is suffering a stroke, the immediate concern is getting them stabilized. Once the initial attack has passed, additional treatment and preventive measures can be implemented. Understanding what’s happening during the actual event, and in the subsequent hours and days, will help improve the effectiveness of the post-attack treatment plan, and also help identify methods of neuroprotection—that is, administer treatments to protect against a stroke in advance for potentially at-risk individuals. Computational biology researchers at Pacific Northwest National Laboratory developed a model for predicting what’s happening during a stroke, how the process evolves over time, the potential outcomes, and the effects of different treatment options.
The work was featured in the journal PLOS Computational Biology
Why It Matters: The ability to examine strokes and other biological processes, through the use of computer simulations rather than after the fact on actual organisms, may significantly accelerate how quickly discoveries can be made in fighting diseases. The ability to model and simulate different treatments prior to administering them to a patient can help predict with more certainty which therapeutic approaches may be the most effective.
"This is the first step in being able to suggest {to health care providers} that if you do X and Y, you’d get a much bigger effect than what you’re currently doing,” said Dr. Jason McDermott, a PNNL computational biologist and lead author on the paper.
Methods: The team developed novel mathematical approaches for extending existing methods of determining causal relationships between genes that are driving biological processes. They implemented ordinary differential equations—a process for describing how things change over time—to improve their ability to infer what these gene relationships might look like and to allow more dynamic simulation of these biological processes over time.
What’s Next: The team is looking at improving the model to simulate events that are happening during a biological process for which there isn’t pre-existing data. Additionally, they plan to test the effect of adding drugs to a treatment plan and also will be looking at micro RNA molecules that currently aren’t included in the model.
The man whose brain ignores one half of his world
Alan Burgess doesn’t need a rhyme to remember the 5th of November. He’ll never forget the day he had his stroke. It left him with a syndrome known as hemispatial neglect and a strange new perspective.
I asked him how he explains this to other people. “I say it’s two different worlds,” says Burgess. “My old world finished on 5 November 2007 and the new world started the same day.”
His stroke damaged the parietal lobe on the right side of his brain, the part that deals with the higher processing of attention. The damage causes him to ignore people, sounds, and objects on his left.
"Hemispatial neglect typically occurs after a stroke," says Dr Paresh Malhotra, senior lecturer in neurology at Imperial College London. "It is not blindness in one eye, and it’s not damage to the primary sensory cortex, it’s a process of ignoring, for want of a better word, one side of space."
(Image credit: zeably.com)