Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R

Background: Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. Objective: To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-kappa B) and nuclear factor-erythroid-related factor-2 (Nrf2). Methods: Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n = 64) as a cerebral I/R injury model. In the MCAO + CUR group, the rats were administered curcumin (300 mg/kg BW, i.p.) at 30 min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24 h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-kappa B and Nrf2 expression levels were assayed through immunohistochemistry. Results: Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-kappa B expression was enhanced in the MCAO group. However, in the MCAO + CUR group, the upregulation of Nrf2, an anti oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-kappa B expression. Conclusion: The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-kappa B. (C) 2015 Elsevier Inc All rights reserved.