We found that SB216763 particularly evoked a powerful induction of SOD2, and increased the antioxidant defense in oxygen-deprived neurons. PGC 1a can Icotinib potently induce endogenous antioxidant genes. This entirely prevented the generation of mitochondrial superoxide. Constant increased superoxide development plays a vital role in the pathophysiological cascade resulting in ischemic neuronal injury and does occur within the peri infarct place after the on-set of pMCAO. Amazingly, SB216763 behaved like a appropriate neuroprotectant in mice subjected to focal cerebral ischemia. We found a biphasic dose response in SB216763 mediated neuroprotection, with optimal impact at intermediate doses, without evidence of change toward toxicity at higher doses. Such Ushaped dose response curves have already been previously observed for other GSK Gene expression and 3b modulators are not unusual in the setting of stroke studies in animals, as recently discussed with implications for drug development. SB216763 is previously reported to cross the blood-brain barrier after intraperitoneal injection. Though persistent pharmacological inhibition of GSK 3 lowers elevated blood glucose in diabetic rodents, intense intravenous application of SB216763 did not modify blood glucose levels nor mean arterial pressure up-to 2 h after center ischemia reperfusion in diabetic or non diabetic rodents, suggesting that the better outcome of cerebral ischemia noticed in our study isn’t influenced by confounding systemic effects. Glycogen synthase kinase 3b is increasingly being accepted as a nice-looking target for drug discovery, with prominence in the treatment of neurological disorders. The multiple functions of the enzyme in various signalling pathways raise the problem of selectivity. Strongest GSK 3 inhibitors also prevent Cdks because of the substantial homology of the ATPbinding sites. This is valid also for BIO and SB216763 at higher doses. However, SB216763 and BIO are many times more selective for Everolimus RAD001 GSK 3 than for Cdks. AR A014418 is regarded as being one of the most selective GSK 3b inhibitor molecules. Further, there’s abundant evidence that double GSK 3/Cdk inhibitors could be desirable for ischemic stroke therapy. An important requirement is that, to prevent past fails in translational swing medicine, potential methods to neuroprotection in cerebral ischemia consider polytherapies or drugs exhibiting a broad action style at various points of the pathologic ischemic cascade. Among possible choice medications, GSK 3 inhibitors deserve special interest. Previous reports have demonstrated that GSK 3b inhibition exerts its favorable effects in the level, by modulating Bcl 2 family proteins and increasing the ROS tolerance for mitochondrial permeability transition pore opening.