SB216763 stopped OGDmediated mitochondrial superoxide production. mRNA levels of antioxidant enzymes analysed by means of quantitative RT PCR 3 h after OGD. While our do not conclusively demonstrate that the Cabozantinib XL184 mitochondrial biogenic effect of medicinal GSK 3 inhibitors has a causative role in neuroprotection, time course of recovery of reduced mitochondrial biogenesis is highly suggestive for this interpretation. Inhibition of ROS generation, which really is a recognized effect of mitochondrial biogenesis, might be also involved in this protective mechanism. The mitochondrial biogenic programs have been found to augment tolerance to cardiac ischemia and have been suggested as new targets for therapeutic interventions to deal with ischemic heart disease. Recently, flexible mitochondrial biogenesis has been explained in the context of cerebral hypoxic pre-conditioning or neonatal hypoxia/ischemia. Nevertheless, versatile phenomena observed after acute temporary hypoxia might differ from the reaction to prolonged hypoxia. More, the endogenous mitochondrial biogenic volume is reduced with aging, so that it hardly could achieve an efficient adaptive reaction to severe hypoxia/ ischemia Meristem in adult or aged people. After a severe ischemic insult, mitochondria may undergo uncontrolled autophagy and oxidative injury. In these circumstances, the reduction of mtDNA information, as noted by others and today’s study, attests the inadequacy of adaptive mitochondrial biogenesis. Indeed, our in vitro studies suggest that impaired mitochondrial biogenesis plays a role in the reduced amount of mitochondrial size and function after cerebral ischemia. The cellular and molecular pathway leading to the down regulation of PGC 1a and downstream targets by cerebral ischemia deserve to be examined. Article ischemic actions of calpain hsp inhibitor proteases, could potentially cause PGC 1a degradation. Aberrant GSK 3b hyperactivation due to increased Tyr216 phosphorylation or even to calpain mediated N final bosom may also reduce PGC 1a levels in ischemic neurons. In keeping with previous reports, we found that GSK 3b inhibition improves neuronal PGC 1a protein levels. As PGC 1a is a strong inducer of NRF 1 gene expression, NRF 1 levels could possibly be consequently augmented. The latter phenomenon might also be caused by improved nuclear factor erythroid 2 associated factor 2 mediated NRF 1 transcriptional control being an indirect consequence of GSK 3b inhibition. The mitochondrial biogenesis program is activated by the coordinated action of PGC 1a and NRF 1. Of interest, we found that SB216763 is able to activate this method also under ischemic conditions, allowing the recovery of satisfactory mitochondrial mass and function. By stimulating mitochondrial electron transport, efficient revival of mitochondria per se may facilitate the decrease in mitochondrial ROS generation.