Administration of melatonin after onset of ischemia reduces the volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model.
OBJECTIVE
In both permanent and transient 3-hour middle cerebral artery occlusion rat stroke models, a single intraperitoneal injection of melatonin at 5 or 15 mg/kg given before ischemia was shown to reduce infarct volume at 72 hours. The present study was conducted to examine the treatment time window when melatonin was commenced after onset of ischemia.


METHODS
Adult male Sprague-Dawley rats were anesthetized to undergo right-sided middle cerebral artery occlusion for 3 hours. A single intraperitoneal injection of vehicle or melatonin at 5 mg/kg was given at 0, 1, or 3 hours after onset of ischemia. Other groups received multiple injections of vehicle or melatonin at 5 mg/kg with the first injection given at 1, 2, or 3 hours after onset of ischemia and the second and third injections at 24 and 48 hours, respectively. Multiple injections of melatonin at 15 mg/kg with the first injection given at 3 hours were also made. The infarct volume was determined at 72 hours.


RESULTS
A single dose of melatonin at 5 mg/kg given at 0 or 1 but not 3 hours after onset of ischemia reduced the infarct volume. Multiple doses of melatonin at 5 mg/kg also reduced the infarct volume when the first dose was given at 1 or 2 but not 3 hours after onset. Significant hemodynamic effects were not observed.


CONCLUSIONS
Our results indicate that melatonin at 5 mg/kg given as a single injection or multiple injections protects against focal cerebral ischemia when commenced within 2 hours of onset.
Pei
Zhong
Z
Division of Neurology, University Department of Medicine, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Pang
Shiu Fun
SF
Cheung
Raymond Tak Fai
RT
D000818:Animals; D001929:Brain Edema / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors
D018696:Neuroprotective Agents; D008550:Melatonin