title: Delayed treatment with melatonin enhances electrophysiological recovery following transient focal cerebral ischemia in rats.
abstract: Melatonin has been reported to reduce infarct volumes induced by transient middle cerebral artery (MCA) occlusion. We examined whether melatonin could improve electrophysiological and neurobehavioral recoveries in rats after 72 hr of reperfusion following 1.5 hr of MCA occlusion. Melatonin (5 mg/kg) or vehicle was given intravenously at the commencement of reperfusion. Neurobehavioral outcome was serially examined, and somatosensory evoked potentials (SSEP) were recorded prior to ischemia and at 72 hr after the onset of reperfusion. Brain infarction was assessed upon killing. Before ischemia-reperfusion, stable SSEP waveforms were consistently recorded after individual fore- or hindpaw stimulation. The amplitude between the first positive (P1) and the first negative (N1) peaks and the P1 latency did not differ significantly between controls and melatonin-treated animals. At 72 hr of reperfusion, controls had severely depressant SSEPs recorded from ischemic fore- and hindpaw cortical fields, and the amplitudes decreased to 36 and 35% of baselines, respectively (P < 0.001). These animals also had transcallosal electrophysiological diaschisis in the SSEPs recorded at the contralateral hindpaw cortical field (P < 0.01). Relative to controls, melatonin-treated animals not only had significantly improved amplitudes of the SSEPs recorded from both ischemic fore- and hindpaw cortical fields, by 33 and 37% of baselines, respectively (P < 0.001), but also exhibited diminished transcallosal electrophysiological diaschisis following ischemia-reperfusion. In addition, melatonin improved sensory and motor neurobehavioral outcomes by 40 and 28%, respectively (P < 0.001), and reduced cortical and striatal infarct sizes by 32 and 40%, respectively (P < 0.05). Thus, delayed intravenous administration with melatonin both enhances electrophysiological and neurobehavioral recoveries and reduces cortical and striatal infarct sizes after cerebral ischemia and reperfusion injury.
authors.affiliation: Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, Institute of Biomedical Engineering, National Cheng Kung University Medical Center and Medical School, Tainan, Taiwan. ejian@mail.ncku.edu.tw
authors.forename: E-Jian
authors.initials: EJ
authors.lastname: Lee
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lee
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Chen
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Tsai
authors.forename: Jih-Ing
authors.initials: JI
authors.lastname: Chuang
authors.forename: Guan-Liang
authors.initials: GL
authors.lastname: Chang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004594:Electrophysiology / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
chemical_list: D008550:Melatonin