Melatonin reduces brain damage after ischemic stroke in diabetic rats

Abstract

Background and Aims: To determine whether administration of melatonin would be neuroprotective against ischemic stroke in diabetic rats. Methods: Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) were induced by streptozotocin alone and a combination of high-fat diet with streptozotocin, respectively. Middle cerebral artery occlusion (MCAO) was performed in T1DM, T2DM, and non-diabetic (non-DM) rats and reperfusion was allowed for 24 or 72 hours before the rats were assessed and sacrificed. Melatonin or vehicle was administered at 30 minutes before ischemia in the group of 24-hour reperfusion, and at 30 minutes before ischemia, 24 hours and 48 hours after reperfusion in the group of 72-hour reperfusion. Results: Compared with non-DM controls, T1DM increased the relative infarct volume by 17.7% and 46.7% (P < 0.05) after MCAO followed by 24-hour and 72-hour reperfusion, respectively; while the infarct volume did not increase in T2DM rats. A single injection of melatonin at 5mg/kg or 10mg/kg reduced the relative infarct volume by 19.7% and 25.6%, respectively (P < 0.01) in T1DM rats after 24-hour reperfusion when compared with the vehicle controls. The neurological performance also improved (P < 0.05). After 72-hour reperfusion, multiple injections of melatonin (5mg/kg) lowered the relative infarct volume by 29.4% (P < 0.01), reduced the edema ratio by 58.0% (P < 0.01) and improved the neurological performance in T1DM rats compared with the vehicle controls. In T2DM rats, melatonin treatment (5mg/kg) reduced the relative infarct volume by 24.45% (P < 0.05) and 27.6% after 24-hour or 72-hour reperfusion, respectively. Conclusions: Melatonin has a neuroprotective effect against ischemic stroke in diabetic rats.