Effect of Melatonin on Expression of c-Jun Proteins and BDNF mRNA in Transient Global Ischemia-Reperfusion Injury of Rat Brain

ABSTRACT

PURPOSE: The purpose of this study was to investigate the effect of systemic treatment of melatonin known as a potent free radical scavenger on expression of c-Jun proteins and brain-derived neurotrophic factor (BDNF) mRNA in transient global ischemia-reperfusion injury of rat brain. METHODS: Spargue-Dalwey rats were used and divided into three groups ischemia group, ischemia group pretreated with melatonin, ischemia group posttreated with melatonin. Brain ischemia-reperfusion injury induced by occlusion of bilateral carotid and vertebral arteries (4-vessel occlusion) for 15 min followed by recirculation of cerebral blood flow. Animals were received intraperitoneal injection of melatonin (10 mg/kg) either 30 min before ischemia (pretreatment) or 0 min after reperfusion (posttreatment). Four vessel occlusion-reperfusion produced ischemic injury in major forebrain structures such as striatum, cortex, hippocampus in the finding of triphenyltetrazolium chloride (TTC) staining. Spectrophotometric assay for formazan, an end-product of TTC showed increased value of formazan formation in ischemic area of the brain posttreated with melatonin 24 hours after the ischemia-reperfusion injury. RESULTS: Posttreatment with melatonin caused a significant decreased in number of c-Jun immunoreactive neurons in CA1 region of the hippocampus after ischemia-reperfusion insult. Furthermore, autoradiographic density for BDNF mRNA in the hippocampus and cortex was increased by systemic treatment with melatonin especially in posttreatment group. CONCLUSION: These results suggest that melatonin treatment results in an attenuation of ischemic damage caused by ischemia-reperfusion in nueronal cells of the sensitive areas of rat brain.