Grant: Project Grant

Stroke constitutes a major cause of death and disability of the adults in Canada, imposing considerable burden on society and economy. Currently, no efficient therapy exists. The cerebral blood vessels form with the nerve cells a functional interface that enables proper brain functioning. The interface comprises multifunctional perivascular cells located between nerve cells and vessels, called pericytes. Emerging reports are suggesting that pericytes contribute to brain repair after stroke by giving rise to other brain cell types, namely nerve and vascular cells. Our findings suggest that the reparative potential of pericytes is regulated by low-oxygen sensitive mechanisms, which are induced after stroke due to blood interruption. Our findings suggest as well that targeting pericytes using pharmacological and cell-based approaches stimulates brain regeneration. The project will dissect how low-oxygen sensitive mechanisms regulate the intrinsic capacity of pericytes to convert to other cells types to compensate for the lost brain tissue. Furthermore, the project will explore novel therapeutic interventions to promote recovery by exploiting the reparative capabilities of pericytes. To achieve these objectives, clinically relevant animal stroke models in which low-oxygen sensitive mechanisms are genetically modified in pericytes will be used. Furthermore, novel cell transplantation approach will be applied by delivering into the brain via the intranasal cavity pericytes modified to convert to nerve and vascular cells. The expected results will provide new fundamental insights into how low-oxygen sensitive mechanisms regulate the reparative capabilities of pericytes, and will highlight new cell-based therapeutic avenues for stroke that can be safely used in patients.