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Neuroprotective Effects of Liraglutide for Stroke Model of Rats
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan
Department of Neurosurgery, Tokai University, Tokyo 151-0063, Japan
Center for Innovative and Translational Medicine, Kochi University Medical School, Nankoku 783-8505, Japan
Department of Neurosurgery, University of South Florida College Medicine, Tampa, FL 12901, USA
* Author to whom correspondence should be addressed.
Received: 2 September 2013; in revised form: 18 October 2013 / Accepted: 23 October 2013 / Published: 30 October 2013
Abstract: The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.
Keywords: cerebral ischemia; diabetes mellitus; glucagon-like peptide-1; liraglutide; oxidative stress; stroke; VEGF
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Sato, K.; Kameda, M.; Yasuhara, T.; Agari, T.; Baba, T.; Wang, F.; Shinko, A.; Wakamori, T.; Toyoshima, A.; Takeuchi, H.; Sasaki, T.; Sasada, S.; Kondo, A.; Borlongan, C.V.; Matsumae, M.; Date, I. Neuroprotective Effects of Liraglutide for Stroke Model of Rats. Int. J. Mol. Sci. 2013, 14, 21513-21524.
Sato K, Kameda M, Yasuhara T, Agari T, Baba T, Wang F, Shinko A, Wakamori T, Toyoshima A, Takeuchi H, Sasaki T, Sasada S, Kondo A, Borlongan CV, Matsumae M, Date I. Neuroprotective Effects of Liraglutide for Stroke Model of Rats. International Journal of Molecular Sciences. 2013; 14(11):21513-21524.
Sato, Kenichiro; Kameda, Masahiro; Yasuhara, Takao; Agari, Takashi; Baba, Tanefumi; Wang, Feifei; Shinko, Aiko; Wakamori, Takaaki; Toyoshima, Atsuhiko; Takeuchi, Hayato; Sasaki, Tatsuya; Sasada, Susumu; Kondo, Akihiko; Borlongan, Cesario V.; Matsumae, Mitsunori; Date, Isao. 2013. "Neuroprotective Effects of Liraglutide for Stroke Model of Rats." Int. J. Mol. Sci. 14, no. 11: 21513-21524.