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

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.

Neuroprotective Mechanisms of Glucagon‐like Peptide‐1‐based Therapies in Ischaemic Stroke: A Systematic Review based on Pre‐Clinical Studies

“…The timing of drug administration varied between studies. Eight studies administered GLP‐1RAs pre‐ischaemia , eight post‐ischaemia and four both pre‐ and post‐ischaemia . For the seven studies involving DPP‐4Is, one study applied the drugs pre‐ischaemia , one post‐ischaemia and five studies both pre‐ and post‐ischaemia .…”

“…Mouse (C57BL/6), rat (Sprague Dawley/Wistar/Wistar albino) and gerbil (Mongolian) animal models were used (n = 1766). Fifteen studies tested non‐diabetic animals , six used diabetic/hyperglycaemic animals , and six studies included both non‐diabetic and diabetic . Diabetes was induced by streptozotocin , high‐fat diet or genetically modified animal strains including db/db mice , Goto‐Kakizaki rats and hyperglycaemia induced by infusion of 50% dextrose .…”

“…All studies but one used a non‐active vehicle as a control, and some studies also investigated sham‐operated animals , other kinds of GLP‐1‐based therapies , other administration routes or other drug classes . Five studies observed the effects of GLP‐1R suppression using knockout animals or specific short hairpin ribonucleic acid (RNA) sequences to target the GLP‐1R .…”

“…RhGLP‐1 decreased expression of different markers of cerebral damage including S100 calcium‐binding protein B (s100B), neuron‐specific enolase (NSE) and myelin basic protein (MBP) . Exenatide reduced Fluoro‐Jade B‐staining, which marks apoptotic cells .…”

“…Sixteen studies evaluated the effects of GLP‐1RAs on infarct volume and revealed a dose‐dependent effect. In most studies, GLP‐1RAs significantly reduced infarct volume when administered pre‐ischaemia , post‐ischaemia or both . Two studies more extensively investigated the timing of GLP‐1RA administrations post‐ischaemia.…”