Protective effect of rhGLP-1 (7–36) on brain ischemia/reperfusion damage in diabetic rats

• RhGLP-1(7–36) reduced blood glucose in diabetic rats.
• RhGLP-1(7–36) decreased infarction volume in diabetic combined with MCAO/R rats.
• Anti-oxidant maybe a mechanism of the neuroprotective effect of rhGLP-1(7–36).

In recent years, GLP-1 and its analogs have been developed for the treatment of type 2 diabetes. It has been reported that stimulating the GLP-1 receptor can protect neurons against metabolic and oxidative insults, and therefore can be used in the treatment of stroke and Parkinson׳s disease. The present study aimed to examine the neuroprotective effects of rhGLP-1 (7–36) and its possible mechanisms against acute ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in diabetic rats. The type 2 diabetic rat model was established by a combination of a high-fat diet and low-dose streptozotocin (STZ). RhGLP-1 (7–36) (20, 40, 80 μg/kg) was given intraperitoneally before reperfusion. The neuroprotective effects of rhGLP-1 (7–36) were evaluated by changes in neurological deficit scores and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Changes in blood glucose were used to assess hypoglycemic effects. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), inducible nitric oxide syntheses (iNOS) and endothelial nitric oxide syntheses (eNOS) after MCAO/R administration (2 h and 46 h) were examined to investigate the possible mechanisms of RhGLP-1 (7–36). Haematoxylin and eosin (H&E) staining was used for histopathological observation. Compared with the control group, rhGLP-1 (7–36)-treated groups decreased nerve function deficiency scores; significantly reduced infarction volume percentage, MDA, iNOS and blood glucose; and significantly increased SOD, GSH-PX and eNOS. In addition, rhGLP-1 (7–36) groups enhanced the density of surviving neurons and increased vascular proliferation. The current study suggests a neuroprotective effect of rhGLP-1 (7–36) in diabetic MCAO/R rats since anti-oxidative and anti-nitrosative stress effects can contribute to beneficial effects against ischemia/reperfusion injury.