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BioMed Research International
Volume 2015, Article ID 189292, 10 pages
http://dx.doi.org/10.1155/2015/189292
Research Article

Effects of Etanercept against Transient Cerebral Ischemia in Diabetic Rats

1Laboratory of Immunobiochemistry, Department of Clinical Dietetics & Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan
2Laboratory of Organic and Medicinal Chemistry, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan
3Laboratory of Pharmacology, School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan

Received 17 August 2015; Accepted 28 October 2015

Academic Editor: Gelin Xu

Copyright © 2015 Naohiro Iwata 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

Diabetes mellitus is known to exacerbate acute cerebral ischemic injury. Previous studies have demonstrated that infarction volumes caused by transient cerebral ischemia were greater in diabetic rats than in nondiabetic rats. Tumor necrosis factor-α (TNF-α) is a proinflammatory protein produced in the brain in response to cerebral ischemia that promotes apoptosis. Etanercept (ETN), a recombinant TNF receptor (p75)-Fc fusion protein, competitively inhibits TNF-α. Therefore, we evaluated the neuroprotective effects of chronic or acute treatment with ETN on cerebral injury caused by middle cerebral artery occlusion/reperfusion (MCAO/Re) in rats with streptozotocin-induced diabetes. Furthermore, we evaluated the effects of ETN against the apoptosis and myeloperoxidase activity. Single administration of ETN before MCAO significantly suppressed exacerbation of cerebral damage in nondiabetic rats, as assessed by infarct volume. In contrast, the diabetic state markedly aggravated MCAO/Re-induced cerebral damage despite ETN treatment within 24 h before MCAO. However, the damage was improved by repeated administration of ETN at 900 μg/kg/daily in rats in an induced diabetic state. These results suggested that repeated administration of ETN can prevent exacerbation of cerebral ischemic injury in the diabetic state and is mainly attributed to anti-inflammatory effects.