Effect of melatonin on neuronal nitric oxide synthase expressing cells in the brain following global cerebral ischemia

Nitric oxide can be either neuroprotective or neurotoxic depending on which isoform is expressed during global cerebral ischemia. The chronological and spatial distribution and expression of neuronal nitric oxide synthase cells in the brain following ischemia and melatonin administration was studied in Sprague-Dawley rats. Global cerebral ischemia was induced by common carotid artery occlusion for 10 min followed by reperfusion. The rats were divided into three experimental groups. One group received 5 mg kg melatonin 30 min before ischemia, another group received the same dose of melatonin post-ischemia and a third NO ischemia NO melatonin control group. All animals were euthanized 72 h post ischemia, perfusion-fixed with 4% paraformaldehyde in phosphate buffer and the brains removed. Immunopositive neuronal Nitric Oxide Synthase (nNOS) expression was observed in the cerebral cortex, putamen, caudate nucleus, substantia reticularis olfactory bulb, nucleus caudatus, hippocampus and subcallosal cortex. No nNOS positive cells were observes in the cerebellum in any group. The nNOS expression was higher in the noischemia NO melatonin group (220) followed by the post-ischmia melatonin melatonin group (179) and the lowest (148) in the pre-ischemia melatonin group. A neuroprotective role by melatonin in the post-ischemic phase seems to be the mechanism of action associated with NOS activity in ischemic brain injur