Posts tagged ischemic stroke
Articles and news from the latest research reports.
Beating the clock for sufferers of ischemic stroke
A ground-breaking computer technology raises hope for people struck by ischemic stroke (缺乏血性中風), which is a very common kind of stroke accounting for over 80 per cent of overall stroke cases. Developed by research experts at The Hong Kong Polytechnic University (PolyU), this novel application that expertly analyses brain scans could save lives by helping doctors determine if a patient has the life-threatening condition.
The CAD stroke technology is capable of detecting signs of stroke from computed tomography (CT) scans. A CT scan uses X-rays to take pictures of the brain in slices. When blood flow to the brain is blocked, an area of the brain turns softer or decreases in density due to insufficient blood flow, pointing to an ischemic stroke.
As demonstrated by Dr Fuk-hay Tang from the Department of Health Technology and Informatics at PolyU, CT scans are fed into the CAD stroke computer, which will make sophisticated calculations and comparisons to locate areas suspected of insufficient blood flow. In 10 minutes, scans with highlighted areas of abnormality will come out for doctors’ review. Early changes including loss of insular ribbon, loss of sulcus and dense MCA signs can be identified, helping doctors determine if blood clots are present.
Ischemic stroke occurs when an artery to the brain is blocked, cutting off oxygen and essential nutrients being sent to the brain, and brain cells will die in just a few minutes. Clot-busting drugs are effective in minimising brain damage but they should be administered within 3 hours from the onset. Immediate diagnosis and treatment are therefore absolutely essential.
In that sense, a diagnostic tool that can expedite the process will be greatly helpful in saving lives. As Dr Tang shared with us, “The clock is ticking for stroke patients. Medications taken in three hours from the onset of stroke are deemed most effective. Chances of recovery decrease with every minute passing by. It usually takes half an hour for the ambulance to arrive at the hospital, at best. Then, another 45 minutes to 1 hour are needed for CT or MRI scans after the patient has been checked and dispatched for the test, which means some waiting and time will slip by. Afterwards, the brain scan will take another 10 to 15 minutes. If our tool can help doctors arrive at a diagnosis in 10 minutes, the shorter response time will make meeting the target more achievable.”
“It might come in handy for physicians with less experience in stroke,” added Dr Tang, “and patient care can be maintained in hospitals where human and other vital resources are already stretched to the limit.”
The life-saving application can also detect subtle and minute changes in the brain that would escape the eye of even an experienced specialist, slashing the chances of missed diagnosis. False-positive and false-negative cases, and other less serious conditions that mimic a stroke can also be ruled out, allowing a fully-informed decision to be made.
Furthermore, equipped with the built-in artificial intelligence feature, the CAD stroke technology would learn by experience. With every scan passing through, along with feedback from stroke specialists, the application will improve on its accuracy over time.
“It is important to identify stroke patients and help them get the urgent treatment they need,” said Dr Tang. “Prompt and accurate diagnosis is in the forefront of our minds when designing the medical application. Healthcare professionals should focus on what they do best and let us take care of the rest.”
Blood-brain barrier repair after stroke may prevent chronic brain deficits
Following ischemic stroke, the integrity of the blood-brain barrier (BBB), which prevents harmful substances such as inflammatory molecules from entering the brain, can be impaired in cerebral areas distant from initial ischemic insult. This disruptive condition, known as diaschisis, can lead to chronic post-stroke deficits, University of South Florida researchers report.
(Image credit: Mosby’s Medical Dictionary, 8th edition. © 2009, Elsevier)
In experiments using laboratory rats modeling ischemic stroke, USF investigators studied the consequences of the compromised BBB at the chronic post-stroke stage. Their findings appear in a recent issue of the Journal of Comparative Neurology.
“Following ischemic stroke, the pathological changes in remote areas of the brain likely contribute to chronic deficits,” said neuroscientist and study lead author Svitlana Garbuzova-Davis, PhD, associate professor in the USF Health Department of Neurosurgery and Brain Repair. “These changes are often related to the loss of integrity of the BBB, a condition that should be considered in the development of strategies for treating stroke and its long-term effects.”
Edward Haller of the USF Department of Integrative Biology, the coauthor who performed electron microscopy and contributed to image analysis, emphasized that “major BBB damage was found in endothelial and pericyte cells, leading to capillary leakage in both brain hemispheres.” These findings were essential in demonstrating persistence of microvascular alterations in chronic ischemic stroke.
While acute stroke is life-threatening, the authors point out that survivors often suffer insufficient blood flow to many parts of the brain that can contribute to persistent damage and disability. Their previous investigation of subacute ischemic stroke showed far-reaching microvascular damage even in areas of the brain opposite from the initial stroke injury. While most studies of stroke and the BBB explore the acute phase of stroke and its effect on the blood-brain barrier, the present study revealed the longer-term effects in various parts of the brain.
The pathologic processes of stroke-induced vascular injury tend to occur in a “time-dependent manner,” and can be separated into acute (minutes to hours), subacute (hours to days), and chronic (days to months). BBB incompetence during post-stroke changes is well-documented, with some studies showing the BBB opening can last up to four to five days after stroke. This suggests that harmful substances entering the brain during this prolonged BBB leakage might increase post-ischemic brain injury.
In this study, the researchers used laboratory rats modeling ischemic stroke and observed injury not only in the primary area of the stroke, but also in remote areas, where persistent BBB damage could cause chronic loss of competence.
“Our results showed that the compromised BBB integrity detected in post-ischemic rat cerebral hemisphere capillaries — both ipsilateral and contralateral to initial stroke insult — might indicate chronic diaschisis,” Garbuzova-Davis said. “Widespread microvascular damage caused by endothelial cell impairment could aggravate neuronal deterioration. For this reason, chronic diaschisis poses as a therapeutic target for stroke.”
The primary focus for therapy development could be restoring endothelial and/or astrocytic integrity towards BBB repair, which may be “beneficial for many chronic stroke patients,” senior authors Cesar V. Borlongan and Paul R. Sanberg suggest. The researchers also recommend that cell therapy might be used to replace damaged endothelial cells.
“A combination of cell therapy and the inhibition of inflammatory factors crossing the blood-brain barrier may be a beneficial treatment for stroke,” Garbuzova-Davis said.
(Source: research.usf.edu)
Averting the Devastating Effects of Stroke
Researchers at the University of Connecticut Health Center are studying ways to prevent the devastating injuries to the body caused by stroke, a leading cause of serious long-term disability.
One American dies from stroke, sometimes called a “brain attack,” every four minutes. More than five times that many people survive a stroke, and for them, the physical damage it causes can be enormous.
“Stroke often doesn’t kill you, but some patients say they would have rather died than be left with severe disability and not be able to care for themselves,” says Dr. Louise D. McCullough, professor of neurology and neuroscience and director of stroke research. “People can often be disabled from their stroke. They need assistance with feeding and sometimes can’t get out of bed. Many can’t speak or communicate, and this is very isolating. And now we’re seeing an increasing number of stroke survivors as our population ages.”
There are two types of stroke. Ischemic strokes, which account for the vast majority, happen when clots block the blood vessels to the brain and cut off blood flow. Hemorrhagic strokes happen when the wall of a blood vessel breaks and blood leaks into the surrounding brain. Signs of either type of stroke include sudden numbness or weakness of the face or arm or leg, especially on one side of the body, as well as sudden confusion, difficulty speaking or understanding, trouble seeing or walking, dizziness or loss of balance, and/or a sudden severe headache.
McCullough’s research focuses on ischemic stroke. This type of stroke can be treated in an emergency room with “clot-busting” medication called tissue plasminogen activator (tPA), which helps reduce damage to the brain. But tPA can be effective only if given within a few hours of a stroke, and many people don’t immediately realize they are having a stroke and don’t seek help right away. In addition, some people can’t receive tPA because of other health issues.
“Nationwide, only 5 to 8 percent of people who have a stroke get tPA effectively,” she says. “So we’ve been limited in treatment. We’ve never been able to find a drug to protect the brain after stroke. Reperfusion (restoring the blood flow using tPA) is less useful because the brain is already damaged.”
So McCullough’s research involves studying factors such as what contributes to brain injury after a stroke and how it might be reversed. Because women tend to do worse than men in terms of survival and disability, she also is studying the role that hormones play in stroke risk and recovery.
Much of the understanding about stroke and its treatment has stemmed from research in men, but not all of those findings can benefit women, she points out. “Stroke is different in women – how we present, how we respond to drugs, how we recover. Women have a higher risk of stroke, a slower recovery and more cognitive problems. We need to understand the sex differences on a cellular level. For example, cell death occurs by different pathways in the two sexes. We’re trying to figure out why the biology is different and whether that’s important to therapy.”
In addition, women and men respond differently to different types of drugs. McCullough points to basic aspirin as an example of this. In women, a daily dose of aspirin can help prevent stroke but seems to have no impact in preventing heart disease. In men, the opposite is true.
Interestingly, McCullough also has found a correlation between social factors and stroke. In a study funded by the National Institutes of Health (NIH), McCullough is using mouse models to understand the role that social isolation might play in ischemic stroke.
“We’ve found that isolation is as big a risk factor for having a stroke as hypertension (high blood pressure),” she explains. “We also found that if we induce a stroke in a mouse that is isolated from others, the stroke is 40 percent bigger. And three days after a stroke, a mouse that is placed with others does better than a mouse that is alone. So now we’re saying that with hospitalized patients, maybe we should put someone who has had a stroke in a room with, say, someone who has had a hip replacement.”
McCullough earned her medical degree and Ph.D. from UConn’s School of Medicine. She completed an internship, residency and fellowship at Johns Hopkins University in Baltimore before returning to Connecticut after her father, a physicist, suffered a disabling stroke. She hopes her research will help people like her father as well as future generations, including her four children ranging in age from 7 to 13, whose framed artwork covers larger portions of the walls in her office than do the smaller certificates honoring her with Best Doctor awards and Outstanding Teacher recognition.
In a nearby office, Dr. Lauren Hachmann Sansing, assistant professor of neurology, is looking at stroke in another way. Her research focuses on hemorrhagic stroke, the type that results from a ruptured blood vessel in the brain. “This type of stroke is devastating,” she explains. “It affects two million patients a year, and only 50 percent survive it. People may become paralyzed, unable to speak and unconscious due to the mass of blood within the brain.”
This intracerebral bleeding induces an immune reaction in the body in which white blood cells (leukocytes) travel to the brain in response to the injury. Unfortunately, this does further harm by causing brain swelling and actually worsens the cell death caused by the stroke. Sansing has obtained an NIH K08 grant – funds awarded to support the research of new physician-scientists – to study how this immune reaction can be prevented.
“Using a mouse model, we are measuring and quantifying how many leukocytes travel to the brain and how we could block them using certain anti-inflammatory drugs, such as arthritis drugs that target this cell population,” Sansing says. “We are working to determine which pathways are active in patients after a stroke, and we think we are onto something. We’re using drugs already tested in humans, with good safety data, and so we already know the dosing. If we find efficacy in animal models, we can go right to safety in human studies.”
Working to understand and treat this secondary wave of injury after a stroke is an interesting mix of the neurology and immunology courses that Sansing enjoyed as a student. She completed undergraduate studies at Cornell University, her medical degree at SUNY Stony Brook School of Medicine, and a master’s in translational research (which involves converting scientific discovery into health improvement) at the University of Pennsylvania, where she also completed an internship, residency and fellowships in vascular neurology and translational medicine.
“We’re hopeful about our work,” Sansing says. “But there have been many, many treatments for stroke that have worked in animal models but failed to improve outcomes in patients. With the evolution of biomarkers studies and the ability to study proteins and activation in patients, we have a lot of insights into what we should go after as potential targets. Dr. McCullough and I have a large biobank of samples from stroke patients who have donated blood samples to help us study the disease. These samples help ensure that what we study in our animal models is important in our patients.”
Both McCullough and Sansing are involved in active research while also seeing patients, and they say their studies are greatly benefitted by doing both. “It’s like a big puzzle,” Sansing explains. “We create a model, study it, go back to patients, then go back to research. Our overall goal is to someday say we have a new treatment that can make a difference in people’s lives.”
Researchers find far-reaching, microvascular damage in uninjured side of brain after stroke
While the effects of acute stroke have been widely studied, brain damage during the subacute phase of stroke has been a neglected area of research. Now, a new study by the University of South Florida reports that within a week of a stroke caused by a blood clot in one side of the brain, the opposite side of the brain shows signs of microvascular injury.
Stroke is a leading cause of death and disability in the United States, and increases the risk for dementia.
"Approximately 80 percent of strokes are ischemic strokes, in which the blood supply to the brain is restricted, causing a shortage of oxygen," said study lead author Svitlana Garbuzova-Davis, PhD, associate professor in the USF Department of Neurosurgery and Brain Repair. "Minutes after ischemic stroke, there are serious effects within the brain at both the molecular and cellular levels. One understudied aspect has been the effect of ischemic stroke on the competence of the blood-brain barrier and subsequent related events in remote brain areas."
Using a rat model, researchers at USF Health investigated the subacute phase of ischemic stroke and found deficits in the microvascular integrity in the brain hemisphere opposite to where the initial stroke injury occured.
The study was published in the May 10, 2013 issue of PLOS One.
The USF team found that “diachisis,” a term used to describe certain brain deficits remote from primary insult, can occur during the subacute phase of ischemic stroke. The research discovered diachisis is closely related to a breakdown of the blood-brain barrier, which separates circulating blood from brain tissue.
In the subacute phase of an ischemic stroke, when the stroke-induced disturbances in the brain occur in remote brain microvessels, several areas of the brain are affected by a variety of injuries, including neuronal swelling and diminished myelin in brain structures. The researchers suggest that recognizing the significance of microvascular damage could make the blood-brain barrier (BBB) a therapeutic “target” for future neuroprotective strategies for stroke patients.
The mechanisms of BBB permeability at different phases of stroke are poorly understood. While there have been investigations of BBB integrity and processes in ischemic stroke, the researchers said, most examinations have been limited to the phase immediately after stroke, known as acute stroke. Their interest was in determining microvascular integrity in the brain hemisphere opposite to an initial stroke injury at the subacute phase.
Accordingly, this study using rats with surgically-simulated strokes was designed to investigate the effect of ischemic stroke on the BBB in the subacute phase, and the effects of a compromised BBB upon various brain regions, some distant from the stroke site.
"The aim of this study was to characterize subacute diachisis in rats modeled with ischemic stroke," said co-author Cesar Borlongan, PhD, professor and vice chairman for research in the Department of Neurosurgery and Brain Repair and director of the USF Center for Aging and Brain Repair. "Our specific focus was on analyzing the condition of the BBB and the processes in the areas of the brain not directly affected by ischemia. BBB competence in subacute diachisis is uncertain and needed to be studied."
Their findings suggest that damage to the BBB, and subsequent vascular leakage as the BBB becomes more permeable, plays a major role in subacute diachisis.
The increasing BBB permeability hours after the simulated stroke, and finding that the BBB “remained open” seven days post-stroke, were significant findings, said Dr. Garbuzova-Davis, who is also a researcher in USF Center for Aging and Brain Repair. “Since increased BBB permeability is often associated with brain swelling, BBB leakage may be a serious and life-threatening complication of ischemic stroke.”
Another significant aspect was the finding that autophagy — a mechanism involving cell degradation of unnecessary or dysfunctional cellular components —plays a role in the subacute phase of ischemia. Study results showed that accumulation of numerous autophagosomes within endothelial cells in microvessels of both initially damaged and non-injured brain areas might be closely associated with BBB damage.
Autophagy is a complex but normal process usually aimed at “self-removing” damaged cell components to promote cell survival. It was unclear, however, whether the role of autophagy in subacute post-ischemia was promoting cell survival or cell death.
More than 30 percent of patients who survive strokes develop dementia within two years, the researchers noted.
"Although dementia is complex, vascular damage in post-stroke patients is a significant risk factor, depending on the severity, volume and site of the stroke," said study co-author Dr. Paul Sanberg, USF senior vice president for research and innovation. "Ischemic stroke might initiate neurodegenerative dementia, particularly in the aging population."
The researchers conclude that repair of the BBB following ischemic stroke could potentially prevent further degradation of surviving neurons.
"Recognizing that the BBB is a therapeutic target is important for developing neuroprotective strategies," they said.
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)
The most common form of strokes are caused by a sudden reduction in blood flow to the brain (ischemia) that leads to an inadequate supply of oxygen and nutrients. These so-called ischemic strokes are one of the leading causes of death and disability in industrialized nations. If they are not immediately remedied by medical intervention, areas of the brain may die off. In the journal Angewandte Chemie, Korean researchers have now proposed a new approach for supplemental treatment: Ceria nanoparticles could trap the reactive oxygen compounds that result from ischemia and cause cells to die.