(Val~8)GLP-1-Glu-PAL Provides Neuroprotection In Mice Transient Focal Cerebral Ischemia

Objective :To investigate the neuroprotective effects of(Val8)GLP-1-Glu-PAL against cerebral ischemia-reperfusion injury in rats, and to explore its protective mechanism in cerebral ischemia- reperfusion injury.Method :A total of male 72 SD rats were randomly divided into sham operation group,model group and GLP-1-treated group(after MCAO 60 minutes intraperitoneal injection 25nmol/kg). Right middle cerebral artery occlusion was performed using an intraluminal thread for 60 minutes as described previously. The model group received intravenous infusion of 0.9% saline after MCAO at a rate and volume similar to those applied in the DA-treated group. The sham operation group underwent the procedure except for MCAO. The sham operation group, model group and GLP-1-treated group were evaluated for various physiologic parameters,neurologic deficit score, infarct size, and immunohistochemical analyses at several time points(1d,3d,7d) after ischemia.Results :1.Physiologic parameter and neurologic evaluation: The glucose levels of the model group was(5.85±0.15), which compared with the sham operation group and GLP-1-treated group rised(P<0.05), that were related to be stress induced by the stroke. Furthermore,mice of GLP-1-treated group showed better functional recovery than the model group(P<0.05).2.Assessment of cerebral infarct volume: Following neurological and motor function testing at 24 hours post MCAO, animals were euthanized by decapitation, and the brains were removed to determine infarct volume. Compared with the model group,GLP-1-treated group showed that the cerebral infarct size was significantly decreased(P<0.05).3.Immunohistochemical analyses: The effect of GLP-1 was associated with the down-regulation of active Bax、i NOS(P<0.05) and the up-egulation of Bcl-2(P<0.05). The number of these markers was the most until 72 hours after reperfusion,and then tended to decrease.4.Terminal Deoxynucleotidyl Transferase(Td T)-Mediated d UTP-Biotin Nick-End :We evaluated cell death using TUNEL staining. The number of TUNEL-positive cells in model grou model groupp was(27.54±1.27)and(8.30±0.59)in GLP-1- treated group,respectively. The number of TUNEL-positive cells increased until 72 hours after reperfusion, and then tended to decrease. GLP-1 significantly reduced the number of such cells,compared with model group.Conclusion :(Val8)GLP-1-Glu-PAL treatment significantly reduced infarct volume and improved functional deficit. It also suppressed inflammatory response, and cell death after reperfusion.(Val8)GLP-1- Glu-PAL provided neuroprotection against brain damage after cerebral ischemia.