Z. W. and C. M. equally contributed to this work.
Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model
Article first published online: 3 FEB 2012
© 2012 John Wiley & Sons A/S
Journal of Pineal Research
Volume 53, Issue 2, pages 129–137, September 2012
How to Cite
Wang, Z., Ma, C., Meng, C.-J., Zhu, G.-Q., Sun, X.-B., Huo, L., Zhang, J., Liu, H.-X., He, W.-C., Shen, X.-M., Shu, Z. and Chen, G. (2012), Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. Journal of Pineal Research, 53: 129–137. doi: 10.1111/j.1600-079X.2012.00978.x
- Issue published online: 13 AUG 2012
- Article first published online: 3 FEB 2012
- Accepted manuscript online: 11 JAN 2012 11:12AM EST
- Received October 10, 2011; Accepted January 5, 2012.
- early brain injury;
- nuclear factor erythroid 2-related factor 2;
- subarachnoid hemorrhage
Abstract: 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 0.3 mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH + melatonin group, melatonin was administered i.p. at 150 mg/kg at 2 and 24 hr after the induction of SAH. Brain samples were extracted at 48 hr 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.