Protective effect of melatonin upon neuropathology, striatal function, and memory ability after intracerebral hemorrhage in rats.
Since free radicals play a role in the mechanisms of brain injury after hemorrhagic stroke, the effect of melatonin (a potent antioxidant and free-radical scavenger) on outcomes was investigated after intracerebral hemorrhage (ICH) in rats. ICH was induced by clostridial collagenase infusion into the right caudate putamen, and several time points and doses of melatonin were studied. Brain edema and neurological function at 24 h were unchanged in comparison with vehicle-treated groups, in spite of oxidative stress reductions. Repeated treatment with the lower dose of melatonin (5 mg/kg) given at 1 h and every 24 h thereafter for 3 days after ICH, led to normalization of striatal function and memory ability over the course of 8 weeks, and less brain atrophy 2 weeks later. These results suggest that melatonin is safe for use after ICH, reduces oxidative stress, provides brain protection, and could be used for future investigations of free radical mechanisms after cerebral hemorrhage.
Lekic
Tim
T
Department of Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, California 92354, USA.
Hartman
Richard
R
Rojas
Hugo
H
Manaenko
Anatol
A
Chen
Wanqiu
W
Ayer
Robert
R
Tang
Jiping
J
Zhang
John H
JH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D000975:Antioxidants; D005609:Free Radicals; D018696:Neuroprotective Agents; D008550:Melatonin