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Cancer Drug May Prevent Stroke-Related Brain Injury

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A stroke is a sudden loss of brain function, most often prompted by a blood clot that blocks blood flow to the brain and, therefore, deprives it of oxygen. Patients may experience loss of vision, balance, coordination, speech, or the ability to understand speech.

Initially, oxygen deprivation tends to occur in a small area of the brain, but further injury often occurs when a molecule known as vascular endothelial growth factor, or VEGF, becomes active. VEGF exists throughout the body to repair tissue damage due to oxygen deprivation by enhancing the growth of new blood vessels. When VEGF is produced in the brain, usually beginning around three hours following a stroke, brain swelling and further injury often occur.

"This is the reason that doctors often don't know how much permanent brain damage a stroke victim will have for 24 to 48 hours," Cheresh says. "Every stroke is a little different, and it is hard to predict how much swelling, and how many of these [other] events will occur. What we have done in this study is interfere with the pathway leading from VEGF to the mechanism that causes brain damage."

Cheresh and colleagues speculated that inhibiting a family of molecules, collectively known as Src, linking VEGF to brain swelling, could reduce the damage linked to the overproduction of VEGF. They tested this theory by treating both normal and genetically engineered mice with a cancer drug that inhibits Src.

Mice that were genetically deficient in Src were found to have increased protection from stroke, and had less brain damage than normal mice when they did have strokes. Normal mice treated with one dose of the Src-inhibiting drug within six hours of stroke induction had less than half of the brain damage as mice not given the drug.

The researchers will soon begin similar studies with larger animals, and hope to initiate human trials within a year. Those trials will probably evaluate this therapeutic technique in combination with clot-busting drugs, Cheresh says.

"This is a novel therapeutic strategy that, we think, will complement the clot busters," Cheresh says. "At this point, we have only done these tests in mice, but there is no reason to believe that what we have seen in mice will not hold up in human patients."

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