Abstract
Ischemic tolerance showed robust protection in the experimental stroke model, but the molecular mechanisms underlying this phenomenon remain unclear. Gene expression of such factors as heat shock protein and anti-apoptotic protein had been extensively investigated, and furthermore, we recently found that CREB activation plays acrucial role on attenuation of ischemic damage and the acquisition of ischemic tolerance. However, metabolic down-regulation and gene reprogramming has recently attracted much attention because of the common pathways also seen in hypothermia, hibernation and endotoxin tolerance. In addition, endogenous adaptation in cerebral collateral vessels against hypoperfusion and ischemia has now been shown to be arteriogenesis. An increase in shear stress in the pial arteriole induces enlargement of vessel diameters and growth of collateral circulation. Colony stimulating factors have also been shown to accelerate the growth of pial collateral vessels. Arteriogenesis enhancement could be a potential target for mitigating ischemic severity after major cerebral artery occlusion.
