Neuroprotective Effects of rhGLP-1 in Diabetic Rats with Cerebral Ischemia/Reperfusion Injury

Drug Dev Res. 2016 May;77(3):124-33. doi: 10.1002/ddr.21297. Epub 2016 Mar 12.

Abstract

Preclinical Research The aim of the present study was to evaluate the neuroprotective benefits of rhGLP-1 in diabetic rats subjected to acute cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Streptozotocin (STZ)-induced diabetic rats were pretreated with rhGLP-1 (10, 20, or 40 μg/kg ip, tid) for 14 days. During this time, body weight and fasting blood glucose levels were assessed. Rats were then subjected to MCAO 90 min/R 24 h. At 2 and 24 h of reperfusion, rats were evaluated for neurological deficits and blood samples were collected to analyze markers of brain injury. Rats were then sacrificed to assess the infarction volume. rhGLP-1 pretreatment lowered blood glucose levels, improved neurological scores, attenuated infarct volumes, and reduced the blood levels of S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and myelin basic protein (MBP). rhGLP-1 has neuroprotective benefits in diabetic rats with cerebral ischemia/reperfusion injury and could potentially be used as a prophylatic neuroprotectant in diabetic patients at high risk of ischemic stroke. Drug Dev Res 77 : 124-133, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: cerebral ischemia/reperfusion injury; diabetes; rhGLP-1.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Brain Ischemia / blood
  • Brain Ischemia / drug therapy*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Disease Models, Animal
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / pharmacology
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Male
  • Myelin Basic Protein / blood
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Phosphopyruvate Hydratase / blood
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Reperfusion Injury / blood
  • Reperfusion Injury / drug therapy*
  • S100 Calcium Binding Protein beta Subunit / blood
  • Streptozocin
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Myelin Basic Protein
  • Neuroprotective Agents
  • Recombinant Proteins
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Streptozocin
  • Glucagon-Like Peptide 1
  • Phosphopyruvate Hydratase