Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats

Free radicals have been implicated in neuronal injury during ischemia reper fusion in stroke. Therefore, in the present study, melatonin, a potent anti oxidant, was studied in male Wistar rats subjected to 2 h of transient midd le cerebral artery occlusion. Melatonin (10, 20 and 40 mg/kg i.p.) was admi nistered four times in an animal at the time of middle cerebral artery occl usion, 1 h after middle cerebral artery occlusion, at the time of reperfusi on and 1 h after reperfusion. Two hours after reperfusion, rats were euthan ized for estimation of oxidative stress markers (malondialdehyde and reduce d glutathione). The doses of 20 and 40 mg/kg of melatonin significantly att enuated the raised level of malondialdehyde (287 +/- 28, 279 +/- 52 nmol/g wet tissue, respectively) as compared to the levels (420 +/- 61 nmol/g wet tissue) in vehicle-treated middle cerebral artery-occluded rats. There was an insignificant change in levels of reduced glutathione at these doses (95 +/- 42, 88.7 +/- 36 mug wet tissue, respectively) as compared to those in the vehicle-treated middle cerebral artery-occluded rats (108.21 +/- 21 mug /g wet tissue). However, there was an insignificant difference between 20 a nd 40 mg/kg treated rats. Therefore, the dose of 20 mg/kg i.p. was used to evaluate the neuroprotective effect by using diffusion-weighted imaging (30 min after reperfusion), assessing the neurological deficit (24 h after mid dle cerebral artery occlusion) and estimating oxidative stress markers (72 h after middle cerebral artery occlusion). In the 20 mg/kg melatonin-treate d group, percent ischemic lesion volume on diffusion-weighted imaging was s ignificantly attenuated (9.8 +/- 3.9) as compared to that in the vehicle-tr eated group (21.4 +/- 4.7). The neurological deficit was significantly impr oved in the melatonin group (1.8 +/- 0.06) as compared to that in the vehic le-treated (2.9 +/- 0.38) group. The level of malondialdehyde (321.4 +/- 31 nmol/g wet tissue) and reduced glutathione (142.6 +/- 13 mug/g wet tissue) in the melatonin-treated group was also significantly decreased as compare d to the level of malondialdehyde (623 +/- 22 nmol/g wet tissue) and reduce d glutathione (226.6 +/- 19 mug/wet tissue) in the vehicle-treated group. T he present study indicates that melatonin has a neuroprotective action in f ocal ischemia, which may be attributed to its antioxidant property. (C) 200 1 Elsevier Science B.V. All rights reserved.