Neuroprotective effects of liraglutide for stroke model of rats

Kenichiro Sato, Masahiro Kameda, Takao Yasuhara, Takashi Agari, Tanefumi Baba, Feifei Wang, Aiko Shinko, Takaaki Wakamori, Atsuhiko Toyoshima, Hayato Takeuchi, Tatsuya Sasaki, Susumu Sasada, Akihiko Kondo, Cesario V. Borlongan, Mitsunori Matsumae, Isao Date

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)21513-21524
Number of pages12
JournalInternational journal of molecular sciences
Volume14
Issue number11
DOIs
Publication statusPublished - Oct 30 2013

Keywords

  • Cerebral ischemia
  • Diabetes mellitus
  • Glucagon-like peptide-1
  • Liraglutide
  • Oxidative stress
  • Stroke
  • VEGF

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    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. (2013). Neuroprotective effects of liraglutide for stroke model of rats. International journal of molecular sciences, 14(11), 21513-21524. https://doi.org/10.3390/ijms141121513