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Melatonin activates the Nrf2‐ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model

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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.
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Document Type: Research Article

Affiliations: 1: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China 2: Department of Surgery, Suzhou Municipal Hospital, Suzhou, Jiangsu Province, China 3: Department of Neurosurgery, Zhangjiagang Hospital, Soochow University, Suzhou, Jiangsu Province, China 4: Department of Neurosurgery, Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu Province, China 5: Department of Surgery, Taicang People’s Hospital, Suzhou, Jiangsu Province, China

Publication date: September 1, 2012

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