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International Journal of Endocrinology
Volume 2015, Article ID 903186, 9 pages
http://dx.doi.org/10.1155/2015/903186
Research Article

Alpha-Lipoic Acid Attenuates Cerebral Ischemia and Reperfusion Injury via Insulin Receptor and PI3K/Akt-Dependent Inhibition of NADPH Oxidase

Department of Neurology, The Affiliated Fourth Centre Hospital of Tianjin Medical University, Tianjin 300140, China

Received 27 September 2014; Revised 14 February 2015; Accepted 17 February 2015

Academic Editor: Małgorzata Kotula-Balak

Copyright © 2015 Yinhua Dong et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alpha-lipoic acid (ALA) has various pharmacological effects such as antioxidative, anti-inflammatory, and antiapoptotic properties. In the present study, administration of ALA (40 mg/kg, i.p.) for 3 days resulted in a significant decrease in neuronal deficit score and infarct volume and a significant increase in grip time and latency time in Morris water maze at 48 h after middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. ALA also reduced the increased TUNEL-positive cells rate and the enhanced caspase-3 activity induced by MCAO/R. However, the underlying mechanisms remain poorly understood. In this study, we found that ALA could activate insulin receptor and PI3K/Akt signaling pathways, inhibit the expression and activity of NADPH oxidase, and subsequently suppress the generation of superoxide and the augment of oxidative stress indicators including MDA, protein carbonylation, and 8-OHdG. In conclusion, ALA attenuates cerebral ischemia and reperfusion injury via insulin receptor and PI3K/Akt-dependent inhibition of NADPH oxidase.