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Stroke

Description
A stroke occurs when the blood supply to part of the brain is suddenly interrupted or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells. Brain cells die when they no longer receive oxygen and nutrients from the blood or there is a sudden bleeding into or around the brain. The symptoms of a stroke include sudden numbness or weakness, especially on one side of the body; sudden confusion or trouble speaking or understanding speech; sudden trouble seeing in one or both eyes; sudden trouble with walking, dizziness, or loss of balance or coordination; or sudden severe headache with no known cause.

Who is at Risk?

Stroke prevention is still the best medicine. The most important treatable conditions linked to stroke are: treating high blood pressure - eating a balanced diet, maintaining a healthy weight, exercising, and taking drugs to reduce blood pressure; quitting cigarette smoking; managing heart disease - your doctor may prescribe medication to help prevent the formation of clots; controlling diabetes with your doctor; seeking help after Transient Ischemic Attacks - these are small strokes that last only for a few minutes or hours and should never be ignored, but should be treated with drugs or surgery; seeing your doctor if you think you have sleep apnea; obesity - reducing your dietary intake of saturated fats and cholesterol; excessive alcohol intake and illegal drug use; and treating certain blood disorders by prescribing "blood thinners." Risk factors that cannot be changed include age - from age 55 onward, your chances of having a stroke more than double every ten years; gender - the incidence of stroke is about 19% higher for men than for women; race - African Americans and Hispanic Americans have a higher risk of stroke than Caucasians do; and heredity - the risk of stroke is greater in people who have a family history of stroke.

Sources: National Institute of Neurological Disorders and Stroke, Texas Heart Institute, Washington University School of Medicine, American Heart Association

A Potential New Approach To Preventing Stroke Damage
A compound already used to treat severe sepsis could open up a whole new approach for treating stroke, the leading cause of long-term disability in the nation. The research shows that a compound known as activated protein C or APC directly protects brain cells that normally die as a result of stroke by curbing the cells' auto-destruct program. The research, led by Professor Berislav Zlokovic of the University of Rochester and Professor John H. Griffin, Ph.D. of TSRI opens up a new vista in a field where effective treatments are scant. The new work is surprising because it points to an unsuspected ability of APC to directly prevent programmed cell death, which has quietly emerged over the past several years as the key to reducing the effects of stroke.

There is currently only one effective treatment for stroke which reaches only a small percentage of patients, so the researchers are hopeful that this finding will spur further research that could help people who will otherwise have lifelong disability due to a brain attack. The scientists showed that, in mice that had strokes, more than 65 percent of the brain cells that normally would die after a stroke survive because of APC. The compound reduced the neurological impact of the stroke by 91 percent. Stroke, a huge problem, is the third leading cause of death in the nation. The study"s results are very exciting.

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Scientists Report Cryo-em Structure of a Human Platelet Integrin Molecule
TSRI researchers, led by Mark Yeager, M.D., Ph.D., have published the first detailed three-dimensional model for the human platelet integrin alphaIIbbeta3 - a signaling molecule that is important for activating platelets, which leads to a healthy formation of blood clots in response to a cut as well as clots that obstruct blood flow to healthy tissue. Integrins are a broad class of signaling molecules that affect diverse biological processes such as development, angiogenesis, wound healing, neoplastic transformation, and thrombosis.

Though scientists have known for many years that integrins are important in many physiological processes, detailed structural information on these molecules has been elusive. These results will be relevant for the design of new drugs to treat health conditions in which the formation of blood clots is undesirable, such as during heart attacks and strokes. Medical techniques like balloon angioplasty and intracoronary stent implantation are designed to clear blocked arteries but can also cause the formation of thrombi. In fact, several clinical trials have demonstrated that alphaIIbbeta3 inhibitors have benefit in the medical treatment not only for heart attacks but also during angioplasty and stent treatment.

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TSRI Researcher Sets His Sights on Improving Outcome for Stroke Patients
TSRI Associate Professor Gregory del Zoppo, M.D. is pursuing his goal of finding ways to improve the clinical outcome of stroke. Del Zoppo has made significant contributions in the laboratory. For years, doctors focused on the ischemic injury to neurons during stroke, and for logical reasons - a stroke deprives the brain of oxygen-rich blood, the lack of oxygen causes neurons to die, and the loss of neurons leads to all the health problems associated with stroke recovery. There is no question that the blood clots and lack of oxygen are the major insult to the neurons. One of the major problems for the microvasculature during ischemic stroke is that often the protective barriers separating the blood from the brain tissue are broken down. Breakdown of the barriers occurs in the ischemic area and leads to hemorrhaging in the brain, which enhances the injury. Some 65 percent of stroke victims experience some sort of hemorrhaging.

During ischemic stroke, endothelial cells detach from each other and astrocytes, cells with star-like appearance, and the extracellular matrix breaks down. Components of blood, including red cells, leak in the tissue. Other blood cells that produce inflammatory chemicals enter the brain and wreak havoc there, injuring tissue and killing brain cells (including neurons). In the clinic, del Zoppo has designed several clinical trials to look at the effect of blocking the adhesion of granulocytes and other immune cells to endothelial cells - to see if agents that block this adhesion can reduce injury to stroke patients. In the laboratory, del Zoppo is asking more fundamentally if some treatment designed to stop the bleeding might reduce injury is well. Proteases called matrix metalloprotease (MMPs) and other matrix proteases are potential players in the injury process, and, as such, are potential targets for therapy. The scientists are testing MMP inhibitors to see if they prevent the degradation of the matrix in laboratory models. If this succeeds, then eventually a carefully controlled human trial might answer the question of whether MMP inhibitors could preserve brain function.

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Study Uncovers New Sensor - A Potential Target For New Therapies For Obesity And Diabetes, And Implications For Heart Disease And Stroke
In a new study, scientists at The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF) have described for the first time a glucose activated sensor that acts as a switch to decrease production of endogenous glucose in the liver, and increase conversion of glucose to fat for storage in adipose tissue. This dual action makes the sensor, Liver X Receptor, a potential target for new therapies aimed at obesity and diabetes. The research may also have implications for heart disease and stroke. In the study, glucose is shown to stimulate the activity of the Liver X Receptors (LXR) a and b. The LXRs act as sensors of dietary components, orchestrating the body's response to nutrients such as oxysterols (short-lived derivatives of cholesterol) and controlling gene expression linked to cholesterol and fat metabolism. When you eat, glucose pours into the gut and is recognized by LXR in the liver, which then activates expression of the enzymes that turn excess glucose into triglycerides that are stored as fat. The fact that the study demonstrates that LXR does both - it binds to glucose and it induces fatty acid synthesis - is significant and makes LXR a potential target for diabetes and obesity treatments. Scripps Research Assistant Professor Enrique Saez, Ph.D., led the study

In some recent animal studies, activation of LXRs using synthetic molecules also induced regression of atherosclerosis, the clogging, narrowing, and hardening of the body's large arteries and blood vessels that can lead to stroke, heart attack, and eye and kidney problems. Elevated levels of pathogenic cholesterols, also known to bind LXR, are a primary risk for development of atherosclerosis. The integration of glucose sensing and control of lipogenesis by LXR may explain why low-fat/high-carbohydrate diets induce hypertriglyceridemia [an elevated level of triglycerides in the blood]. LXR can sense surplus glucose, induce fatty acid synthesis, and prompt the liver's export of triglycerides into the bloodstream. Since LXR acts as the body's sensor of a buildup of pathogenic cholesterol, its ability to bind both glucose and oxysterols suggests that LXR may be a link between hyperglycemia and atherosclerosis. In fact, Saez and his colleagues originally looked at LXR as a drug target for atherosclerosis. But when they fed synthetic LXR ligands to mice to induce activation, they discovered that the mice metabolized glucose more effectively and that activation suppressed new production of glucose in the liver.

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Scripps Research Team Sheds New Light On How Blood Clots Form – Findings Could Lead To Novel Ways To Prevent Heart Attack And Stroke
Scripps Research Institute scientists have discovered new elements of the blood clot-formation process. The findings could lead to better drugs for preventing heart attacks and other clot-related conditions. The work helps to establish a new model of clot formation.

According to the old model, an injury to the wall of blood vessels causes smooth muscle cells to expose a clot-organizing protein called tissue factor. In the emerging new model, tissue factor exists on the surfaces of these smooth muscle cells, as well as on circulating immune cells, but in an inactive state. Scripps Research Professor Wolfram Ruf, M.D., led the study.  Ruf and his colleagues showed that cell-surface receptor P2X7, which was known to promote inflammation when stimulated, also plays a major role in the clot-forming process by activating tissue factor.

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