Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model
Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms.To date,the relation betweenmelatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models.This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH.Adult male SD rats were divided into four groups:(1) Control group (n =18) ; (2) SAH group (n =18) ; (3) SAH +vehicle group (n =18) ; and (4) SAH + melatonin group (n =18).The rat SAH model was induced by injection of 0.3 ml fresh arterial,non-heparinized blood into the prechiasmatic cistern in 20 sec.In SAH + melatonin group,melatonin was administered i.p.at 150 mg/kg at 2 h and 24 h after the induction of SAH.Brain samples were extracted at 48 h after SAH. Treatment with melatonin markedly increased expressions of Nrf2-ARE pathway related agents,such as Nrf2,heme oxygenase-1 (HO-1),NAD(P)H:quinone oxidoreductase 1 (NQO1),and glutathione S-transferase α-1 (GST-α1).Administration of melatonin following SAH significantly ameliorated EBI,including brain edema,blood-brain barrier (BBB) impairment,cortical apoptosis,and neurological deficits.In conclusion,post-SAH melatonin administration may attenuate EBI in this SAH model,possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes.
Zhong Wang Gang Chen SAH Research Team
Department of Neurosurgery, The First Affiliated Hospital of Soochow University
国内会议
北京
英文
61-61
2012-08-10（万方平台首次上网日期，不代表论文的发表时间）