Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia

Large infarcts develop in pinealectomized rats subjected to middle cerebral artery occlusion, which was attributed to loss of antioxidant action of me latonin. However, melatonin also has vascular actions, and pinealectomy may induce hypertension. The authors investigated (1) whether hemodynamic fact ors contribute to infarct development in pinealectomized rats, (2) whether melatonin administration can reverse the unfavorable effect of pinealectomy on infarct formation, and (3) whether melatonin can reduce the infarct vol ume in nonpinealectomized rats subjected to focal transient ischemia (2 hou rs middle cerebral artery occlusion, 22 hours reperfusion). Rats were pinea lectomized 3 months before ischemia to eliminate any possible action of pin ealectomy-induced hypertension on stroke. Blood pressure and regional CBF v alues during ischemia and reperfusion were not significantly different betw een pinealectomized and sham-operated rats, suggesting that pinealectomy-in duced increase in infarct was not related to hemodynamic factors. The infar ct volume resumed to the level of sham-operated rats on melatonin administr ation. Injection of melatonin (4 mg/kg) before both ischemia and reperfusio n reduced infarct volume by 40% and significantly improved neurologic defic it scores in pinealectomized as well as sham-operated rats subjected to mid dle cerebral artery occlusion. These data suggest that physiologic melatoni n release as well as exogenously given melatonin has a neuroprotective acti on in focal cerebral ischemia.