Melatonin protects against oxygen and glucose deprivation by decreasing extracellular glutamate and Nox-derived ROS in rat hippocampal slices

Therapeutic interventions on pathological processes involved in the ischemic cascade, such as oxidative stress, neuroinflammation, excitotoxicity and/or apoptosis, are of urgent need for stroke treatment. Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CAl and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period. Furthermore, melatonin afforded maximum protection against glutamate-induced toxicity and reversed the glutamate released almost basal levels, at 10 and 30 mu M concentration, respectively. Consequently, we propose that melatonin might strongly and positively influence the outcome of brain ischemia/reperfusion. (C) 2016 Elsevier B.V. All rights reserved.