Neuroscience
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Because of their favorable action profiles in humans, both memantine and melatonin are particularly interesting candidates as neuroprotectants in acute ischemic stroke. Until now, the signaling mechanisms mediating memantine's neuroprotective actions remained essentially uninvestigated. In addition, we have combined memantine with melatonin, which is a well-known neuroprotective molecule. ⋯ Synergistic effects of memantine and melatonin were observed in the inactivation of p21, p38/MAPK and SAPK/JNK1/2 pathways. Moreover, memantine reversed the effects of melatonin on the activation of ERK-1/2 pathway. Here, we provide evidence that free radical scavenger melatonin potentiates the effects of memantine on ischemic brain injury via inactivations of p21 and stress kinases p38/MAPK and SAPK/JNK1/2 pathways.
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Recent studies suggest that normobaric hyperoxia (HO) reduces hypoxia-reoxygenation injury in the rat brain. We have attempted to determine the effect of HO on Na(+)-Ca(2+) exchangers (NCX) in the rat stroke model. ⋯ Although further studies are needed to clarify the mechanisms of ischemic tolerance, HO partly is associated with the expression of NCX1, 2, 3 consistent with an active role in the genesis of ischemic protection.