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 between melatonin 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: (i) control group (n=18); (ii) SAH group (n=18); (iii) SAH+vehicle group (n=18); and (iv) SAH+melatonin group (n=18). The rat SAH model was induced by injection of 0.3mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20s. In SAH+melatonin group, melatonin was administered i.p. at 150mg/kg at 2 and 24hr after the induction of SAH. Brain samples were extracted at 48hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase α-1. 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.
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Zhong
Z
Wang
Chao
C
Ma
Cheng-Jie
CJ
Meng
Guo-Qing
GQ
Zhu
Xue-Bo
XB
Sun
Lei
L
Huo
Jian
J
Zhang
Hui-Xiang
HX
Liu
Wei-Chun
WC
He
Xu-Ming
XM
Shen
Zhang
Z
Shu
Gang
G
Chen
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000517:prevention & control*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology
D051267:NF-E2-Related Factor 2; D008550:Melatonin