title: Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia-reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.
authors.affiliation: Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Teramoto
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Miyamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Yatomi
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Oishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Takao
authors.initials: T
authors.lastname: Urabe
mesh_terms: D000818:Animals; D000242:Cyclic AMP; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D007249:Inflammation; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000242:Cyclic AMP