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The protective effect of ischemic postconditioning (IPostC) against stroke has been well-established, and the underlying mechanisms are known to involve inhibited-inflammation and free radical production. Nevertheless, how IPostC affects protein expression of iNOS, nitrotyrosine, and COX-2 has not been characterized. In addition, the role of the galectin-9/Tim-3 cell signaling pathway-a novel inflammatory pathway-in IPostC has not been studied. We examined whether iNOS, nitrotyrosine, and COX-2, as well as galectin-9/Tim-3 are involved in the protective effects of IpostC in a rat focal ischemia model. Western blot and confocal immunofluoresent staining results indicate that IPostC significantly inhibited Tim-3 expression, and that galectin-9 expression was also inhibited. In addition, IPostC attenuated production of iNOS and nitrotyrosine, but not COX-2, suggesting that IPostC has distinct effects on these inflammatory factors. Furthermore, the inflammation inhibitor minocycline blocked Tim-3 and iNOS expression induced by stroke. Taken together, we show that the galectin-9/Tim-3 cell signaling pathway is involved in inflammation induced by stroke, and IPostC may reduce infarction by attenuating this novel pathway as well as the inflammatory factors iNOS and nitrotyrosine, but not COX-2. [ABSTRACT FROM AUTHOR]

Postconditioning, a series of mechanical interruptions of reperfusion after ischemia, prevents ischemia/reperfusion injury in myocardial infarction. The extensive studies of postconditioning in myocardial infarction have led to clinical trials. This article reviews the protective effects of postconditioning against ischemia from the heart to the brain and provides insights on how studies of postconditioning in the field of heart ischemia have shed light on postconditioning of the brain. Because brain ischemia has many mechanisms in common with heart ischemia, it is logical to test whether postconditioning protects against brain ischemia as well. A few groups have reported that postconditioning reduces infarct size in focal cerebral ischemia and improves deficits of short-term memory and motor coordination after global cerebral ischemia. However, many outstanding issues remain elusive regarding the protective effects of postconditioning against cerebral ischemia. Future studies should further identify parameters that generate the strongest protection for postconditioning against cerebral ischemia and should study whether postconditioning provides long-term protection. In addition, clarification of the underlying protective mechanisms should be pursued. This will certainly enhance our understanding of this novel phenomenon and may provide important clues for developing pharmacological analogues for stroke treatment. [ABSTRACT FROM AUTHOR]

In recent years, the phosphoinositide-3-kinase/Akt cell survival signaling pathway has been increasingly researched in the field of stroke. Akt activity is suggested to be upregulated by phosphorylation through the activation of receptor tyrosine kinases by growth factors. Although the upstream signaling components phosphoinositide-dependent protein kinase (PDK)1 and integrinlinked kinase enhance the activity of Akt, phsophatase and tensin homolog deleted on chromosome 10 (PTEN) decreases it. Upon activation, Akt phosphorylates an array of molecules, including glycogen synthase kinase3β (GSK3β), forkhead homolog in rhabdomyosarcoma (FKHR), and Bcl-2-associated death protein, thereby blocking mitochondrial cytochrome c release and caspase activity. Generally, the level of Akt phosphorylation at site Ser 473 (P-Akt) transiently increases after focal ischemia, whereas the levels of phosphorylation of PTEN, PDK1, forkhead transcription factor, and GSK3β decrease. Numerous compounds (such as growth factors, estrogen, free radical scavengers, and other neuroprotectants) reduce ischemic damage, possibly by upregulating P-Akt. However, preconditioning and hypothermia block ischemic damage by inhibiting an increase of P-Akt. Inhibition of the Akt pathway blocks the protective effect of preconditioning and hypothermia, suggesting the Akt pathway contributes to their protective effects and that the P-Akt level does not represent its true kinase activity. Together, attenuation of the Akt pathway dysfunction contributes to neuronal survival after stroke. [ABSTRACT FROM AUTHOR]