title: Neuroprotective effects of liraglutide for stroke model of rats.
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.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan. tyasu37@cc.okayama-u.ac.jp.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Sato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kameda
authors.forename: Takao
authors.initials: T
authors.lastname: Yasuhara
authors.forename: Takashi
authors.initials: T
authors.lastname: Agari
authors.forename: Tanefumi
authors.initials: T
authors.lastname: Baba
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Aiko
authors.initials: A
authors.lastname: Shinko
authors.forename: Takaaki
authors.initials: T
authors.lastname: Wakamori
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Toyoshima
authors.forename: Hayato
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sasaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Sasada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Matsumae
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000818:Animals; D001786:Blood Glucose; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D000069450:Liraglutide; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1