Neuroprotective Effect of Melatonin on Brain Damage Induced by Acute Global Cerebral Ischemia in Cats

Background nin has been proposed as a neuroprotective agent on the basis of its ability to function as a free radical scavenger, provided that lipoperoxidation and other free radical damage induced by reactive oxygen species resulting from cerebral ischemia are relevant pathophysiologic processes of ischemic neuronal damage. s fects of melatonin or vehicle on neurologic deficit scores (Todd scale; maximal deficit score = 100, daily during 7 days after the ischemic episode) and neuronal population of hippocampal CA1–CA4 fields (cresyl violet stain, at the eighth day after the ischemic episode) were evaluated in adult male cats subjected to a 15-min period of acute global cerebral ischemia induced by cardiorespiratory arrest, and in cats subjected to a sham procedure. Continuous intravenous (iv) administration of either melatonin 10 mg/kg/h in 10% ethanol in saline or the vehicle alone (3 mL/kg/h) for 6 h starting 30 min after the end of the period of global cerebral ischemia was used as treatment. s cerebral ischemia resulted in a severe loss of neurons in hippocampal CA1–CA4 fields (9, 13, 30 and 28% remaining neurons, respectively) of ischemic vehicle-treated cats in comparison with sham cats (100%). By contrast, remaining neurons in these regions were between 81 and 100% in the ischemic melatonin-treated cats, values that are nonsignificantly different as compared with sham cats. Values of remaining neurons in CA1–CA4 fields in ischemic melatonin-treated cats were significantly higher than those in ischemic vehicle-treated cats. Neurologic deficit scores in ischemic vehicle-treated cats (42–77 at day 1, 6–39 at day 7) were significantly higher than those in ischemic melatonin-treated cats (16–38 at day 1, 0–6 at day 7) on the days after the ischemic episode. sions l, the results support the neuroprotective effect of melatonin against the neuronal cerebral damage induced by acute global cerebral ischemia.