Neuroprotective effect of melatonin on cortical impact injury in the rat

The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content. 45 anesthetized male Sprague-Dawley rats (250-350 mg) were subjected to cortical impact injury of moderate severity (7 mis, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated. Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n = 7: 41.9 +/- 5.2 mm(3), melatonin, n = 8: 30.5 +/- 4.2 mm(3), p < 0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n = 8: 42.1 <plus/minus> 5.1 mm(3), melatonin, n = 8: 35.9 +/- 2.2 mm(3), reduction of 15%, p = 0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night.