Insights on stroke from the peripheral blood suggest ways to develop markers and therapies


Since scientists can not easily obtain brain tissue biopsies as people are having strokes, the development of rapid, high resolution brain imaging modalities was a big step forward in gaining a better understanding of the onset and progression of these often catastrophic events. Now scientists at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) are combining real-time imaging technology with yet another way of following what happens during a stroke. Using small blood samples taken from patients' arms during and immediately following strokes, the researchers have found white blood cell genetic changes they believe reflect the body's fighting response to the ongoing "brain attack" of an ischemic stroke.

About 80 percent of all strokes (the other 20 percent being hemorrhagic), ischemic strokes occur when the blood vessel is blocked, depriving brain tissue of blood and the oxygen carried by the blood. In a further finding, leaking antigens from the injured brain may stimulate increased numbers of a particularly toxic type of T cell lymphocyte, which can actually precipitate new strokes by causing damage to the lining of the blood vessels.

Dr. Alison Baird, of the NINDS Stroke Neuroscience Unit, presented the study at Experimental Biology 2004, as part of the scientific sessions of the American Association of Anatomists, one of the six sponsoring societies of this year's Experimental Biology meeting.

Dr. Baird says new insights from the peripheral blood into the pathology of stroke and the body's response to stroke may allow the development of surrogate biomarkers of stroke risk and prognosis and give information on new cellular and pathological mechanisms involved in the etiology and response to acute stroke, ultimately leading to new drug therapies or preventive vaccines.

Blood studies are infinitely faster and more practical than looking at brain tissue samples from biopsy or post-mortem, and have the added advantage of being available serially throughout the ongoing stroke. A few drops of peripheral blood provide complete information on DNA, the switching on and off of genes, and the proteins that are synthesized and secreted into the blood after stroke, as well as the effect of inflammation on stroke.

But what makes the technique so immensely valuable in understanding stroke, says Dr. Baird, is the ability to combine it and correlate data from rapid, high-resolution imaging modalities. With advances like single photon emission computed tomography (SPECT) and particularly Magnetic Resonance Imaging (MRI), it has been possible for the first time to study human ischemic stroke while it is happening, beginning as early as the first half hour after symptom onset.

It was known from animal studies in the late 1970s that there were two distinct zones of damage from ischemic stroke: an "infarct" zone of severely reduced blood flow, or ischemia, that could survive only minutes, and an "ischemic penumbra," tissue located at the edges of the infarct zone which could survive from three to six hours because it drew some oxygen and nourishment from surrounding blood vessels. Those animal findings provided the impetus for development of stroke therapies like the clot-busting tissue plaminogen activators so widely used today, drugs that restore blood flow and thus slow brain death.

The development of functional MRI sequences (continuous images of brain activities) provided valuable new insights into how ischemic stroke progresses in humans during the period of ischemic lesion evolution when the infarct zone is expanding and when giving drugs to restore blood flow is most likely to prevent damage to the brain tissue.

MRI and other imaging modalities also allowed clinicians to detect ischemic lesions as early as the first half hour after symptom onset and differentiate between patients experiencing ischemic stroke, and therefore likely to benefit from clot busting drugs to open up blockage, and patients experiencing or at high risk for hemorrhagic stroke, for whom clot-busting treatment would increase the risk of cerebral bleeding.

Ongoing work in Dr. Baird's laboratory is investigating the association between inflammation and gene expression on ischemic brain tissue and clinical outcomes. Other investigators involved in this work are Violet Wright, Zurab Nadareishvili, Hua Yu and David Moore.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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