New Research into Ischemic Stroke Treatment

A stroke (also called a cerebrovascular accident or CVA) occurs due to reduced blood supply to the brain that results in loss of brain functions. This reduction can be due to ischemia caused by a thrombosis or embolism or due to a hemorrhage,which is the leakage of blood into tissues; hence the terms ischemic and hemorraghic stroke. Ischemic strokes are treated with thrombolysis which serves to dissolve the clot. The current preferred treatment for ischemic strokes is a drug called rtPA (recombinant tissue plasminogen activator). As with most stroke drugs, rtPA must be administered within the first few hours of a stroke or the risks of treatment outweigh the benefits. A potential risk involves a sudden rise in blood pressure due to the dissolving of the clot, which can subsequently lead to blood vessel rupture and bleeding into the brain.

Less than 10% of stroke victims will make it to the hospital early enough to be treated with rtPA. The rest are given drugs that reduce the possibility of futher clot formation but do not dissolve the initial clot. A reason for this includes the diagnosis of the type of stroke by brain scans. Administration of rtPA, or other "clot busters", in hemorrhagic stroke will lead to increased bleeding into the brain.

New research shows that tPA (tissue plasminogen activator) can be released by neurons themselves. In a postulated hypothesis, tPA in small quantities can bind to NMDA receptors. Normally, NMDA receptors allow the influx of sodium and calcium, the latter mechanism being important for learning and memory. But damaged neurons, for example, during stroke, release tPA in large quantities. High levels of tPA can cause neighboring neurons to die, by NMDA-mediated excitotoxicity, and can even damage the blood-brain barrier.

Mechanistically, it is possible to prevent the association of tPA with NMDA receptors by antibody neutralization. In mouse stroke model studies, injection of anti-tPA antibodies resulted in reduced stroke-inflicted brain damage both on its own or in combination with administered rtPA both following stroke and 6 hours later. Using the antibody, not only did the researchers see a decreased level of brain damage but also the antibody seems to work beyond the current critical time window.

Newscientist article: http://www.newscientist.com/article/mg20727682.500-antibody-cuts-brain-damage-in-strokes.html