Neuroprotective effects of liraglutide for stroke model of rats

Int J Mol Sci. 2013 Oct 30;14(11):21513-24. doi: 10.3390/ijms141121513.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Disease Models, Animal
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Humans
  • Infarction, Middle Cerebral Artery
  • Liraglutide
  • Neuroprotective Agents / administration & dosage
  • Oxidative Stress / drug effects
  • Rats
  • Stroke / complications
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Stroke / pathology
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Blood Glucose
  • Neuroprotective Agents
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Liraglutide
  • Glucagon-Like Peptide 1