Grant: Operating Grant

Stroke is the leading cause of permanent neurological disability in Canada with over 50,000 new cases annually. There are no current medical therapies for alleviating the chronic functional impairments following stroke. The identification of multipotent neural stem cells in the adult mammalian brain has spurred significant interest regarding the potential for stem cell therapy to treat neurological injury or disease. However, activating resident stem cells in the brain has proven to be insufficient to promote repair and combinatorial strategies such as using drugs and small molecules to enhance the repair process, are required. Similarly, rehabilitation has tremendous impact on recovery, but not enough to achieve complete repair. In this proposal we will explore the ability of stem cell activation, rehabilitation and the combination of both strategies, to repair the injured brain following stroke. Most important we will apply our strategies to treat cognitive impairment, which is one of the most frequent and devastating outcomes for victims of stroke. Despite the prevalence and importance, little work has been done towards developing tools to enhance cognitive repair. Further, nearly all stroke studies are performed in young animals in spite of the fact that the incidence of human stroke rises appreciably in middle age and neuroplasticty declines across the life span. Herein we will explore the efficacy of our combined strategies in young, and then older animals. We will significantly increase the clinical relevance of our studies by further engineering a novel system to deliver drugs directly to the brain to achieve stem cell activation. Hence, in combination with rehabilitation strategies, we will achieve interventions for the treatment of stroke that can be translated to the clinic.