Grant: Project Grant

Stroke is the third leading cause of death in North America, the leading cause of disability, and it represents a huge socioeconomic stress. Stroke is a sudden loss of blood supply to brain that occurs when the blood supply to a specific part of the brain is suddenly interrupted (ischemic) or when a blood vessel in the brain either bursts or is blocked. Brain tissue dies when it no longer receives oxygen and nutrients from the blood, leading to the symptoms and disabilities seen in stroke patients. As it stands, we lack effective pharmacotherapy that directly protects brain cells from stroke insults. Our objective is to achieve a better understanding of the molecular mechanisms by which stroke insults produce brain cell damage and thereby develop novel pharmacotherapies. Using a combination of computer-aided in silico receptor modeling, chemical library screening, and functional characterization, we have recently identified a small molecule (BRC-619) that can specifically activate NMDA receptor on the neuronal surface in a subunit specific manner, thereby promoting intrinsic neuronal survival signaling. Using cellular and animal models of stroke, we were able to provide preliminary results showing that this new drug can significantly reduce stroke-induced brain cell death. We propose further validation using several animal models of stroke to determine if the new drug we developed can be used as a new and effective post-stroke pharmacotherapy. We expect that the completion of our proposed study will help to bring this drug to the point where it can be tested in human stroke patients. Our research can be expected to lead to better stroke therapies and hence, will directly impact the health of Canadians by reducing mortality and morbidity from stroke.