Executive Summary : | Stroke remains the second leading cause of deaths worldwide, with India experiencing 1.17 million new cases and 0.7 million deaths in 2016. Tissue plasminogen activator is the only treatment option with limited use. Heme oxygenase-1 (HO-1) is an inducible enzyme involved in the degradation of pro-oxidant heme to antioxidant biliverdin, carbon monoxide, and free iron. Numerous in-vivo and in-vitro evidences have shown neuroprotective effects of increased expression of HO-1 after ischemic stroke, and HO-1 knockout exacerbated brain damage. In clinical studies, increased HO-1 levels have been reported in serum and post-mortem brain samples. Targeting and modulating HO-1 in ischemic stroke seems to be a promising therapeutic strategy. Stroke evolves rapidly, and there is a need to target at the specific time-point to control the succeeding processes of ischemia/reperfusion injury. However, there is a gap in spatio-temporal expression profile of HO-1 and its correlations with stroke outcome, including its role in long-term recovery. The proposed study aims to explore the therapeutic potential of HO-1 as a target for ischemic reperfusion injury by studying its spatio-temporal expression profile (cell types in cortex and striatum and at different time points of reperfusion). The results will generate novel data about site-specific, cell-specific, and time-dependent changes in HO-1 expression at different phases of stroke, helping future studies in targeting HO-1 more efficiently and exploring its true translational potential for ischemia/reperfusion injury. |