Physical exercise regulates neural stem cells proliferation and migration via SDF-1α/CXCR4 pathway in rats after ischemic stroke

Physical exercise is beneficial to functional recovery after stroke. But its underling mechanism is still unknown. It is reported that neural stem cells (NSCs) proliferation, migration and differentiation play an important role in recovery following stroke, furthermore, stromal cell derived factor-1α (SDF-1α) and its chemokine receptor type 4 (CXCR4) regulate NSCs migration. This study is aimed to examine whether physical exercise improves functional recovery by enhancing NSCs proliferation, migration and differentiation through SDF-1α/CXCR4 axis in rats after ischemic stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with physical exercise after MCAO. AMD3100 (an antagonist of CXCR4) was used to confirm the effect of SDF-1α/CXCR4 axis on exercise-mediated NSCs mobilization. We found that physical exercise improved functional recovery and reduced infarct volume. Moreover, 5-bromo-2′-deoxyuridine (BrdU), doublecortin (Dcx)-positive cells in the ipsilateral SVZ and BrdU/neuron-specific nuclear protein (NeuN)-positive cells in the ipsilateral striatum were increased by physical exercise. Simultaneously, SDF-1α-positive cells were significantly higher in physical exercise group than those in control group. Our results indicate that physical exercise improves functional recovery in ischemic rats possibly by enhancement of NSCs proliferation, migration in the SVZ and differentiation in the damaged striatum. Moreover, SDF-1α/CXCR4 pathway involves in exercise-mediated NSCs proliferation and migration but not differentiation.