Figure 1.

Diagrammatic representation summarizing the different mechanisms employed in the preconditioning exercise-induced neurovascular protection in stroke. Preconditioning exercise may induce neurovascular protection by reducing post-stroke expression and activation of inflammatory cytokines like tumor necrosis factor alpha (TNFα), interleukins (ILs), and nuclear factor kappa B (NF-κB), which in turn reduces post-stroke inflammation; [44-53] increasing the expression of vascular endothelial growth factor (VEGF), VEGF receptors, caveolin, and angiopoietin in the brain, which in turn may increase angiogenesis and neovascularization;[56-58] reducing post-stroke expression and activation of matrix metalloproteases (MMPs) and increasing the expression of integrins proteins which may reduce blood-brain barrier (BBB) disruption;[46-48,54,55] increasing endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production which may increase post-stroke cerebral blood flow (CBF);[62-64] increasing expression and activation of hypoxia-inducible factor 1 alpha (HIF-1α), heat shock proteins (HSPs), brain derived neurotrophic factor (BDNF); and inhibition of glutamate and caspase activities which may increase neurogenesis and reduce neuronal death through.[68-86] Collectively, these mechanism may lead to reduction in brain infarction and edema, reduction in BBB disruption and improvement in neurological and functional outcomes.