Grant: China-Canada Joint Health Research Initiative

Stroke is a leading cause of disability and death worldwide. It affects about 50,000 Canadians each year, and about 1% of Canadians are living with the effects of stroke. About 80% of strokes are ischemic, which is caused by the interruption of blood flow to the brain and often results in massive death of brain cells (neurons) and consequently loss of neurological functions. There are two types of cell death in ischemic stroke: acute neuronal death that occurs quickly after a stroke and delayed neuronal death that occurs hours to days after a stroke. The delayed neuronal death is a hallmark feature of ischemic stroke and the primary target for neuroprotective strategies. Previously, others and we have shown that a death-inducing gene called BNIP3 plays an important role in causing the delayed neuronal death. Recently, we have obtained evidence that BNIP3 selectively causes damage to mitochondria, the chemical plant of the cell, leading to cell death. Blocking the BNIP3 cell-death pathway, therefore, is a new strategy for rescuing these neurons and improving the recovery of neurological functions following strokes. The experiments proposed here are built on our previous studies to further understand how BNIP3 induces neuronal cell death following stroke and to develop and test new approaches to protect neurons from death by inhibiting the activity of the death-inducing gene BNIP3. The outcome of the project will provide important insights into mechanisms of delayed neuronal death and new strategies for neuroprotection that can be translated to bedside care of stroke