Pharmaceutical Agents to Reduce Poststroke Brain Injury

Cerebral ischemia as a consequence of stroke often produces irreversible brain damage andpermanent functional disability. There is presently no practical treatment for such ischemic brain injury.Certain neurotrophic proteins have been shown to have beneficial neuroprotective effects whenadministered after experimental stroke in laboratory animals, but these proteins are unlikely to be usefultherapeutic agents; they cannot be delivered expeditiously to stroke-affected brain regions because ofexclusion by the blood brain barrier. We have developed two candidate neuroprotective agents whichit feels will be of great practical value in this area. The neuroprotective activity of these agents has beendemonstrated in vitro, and evidence indicates that they will gain access to the brain after-systemicadministration. We will outline a research program intended to demonstrate the efficacy of these agentsin protecting against ischemia-induced brain injury in vivo. Gerbils will be subjected to cerebral ischemiaby carotid artery occlusion and treated with NMI's candidate neuroprotective agents. The agents'efficacy will be determined by monitoring behavior known to be influenced by ischemic brain injury andby histological analysis of key regions of the gerbil brains.