Delayed Administration of the Glucagon-Like Peptide 1 Analog Liraglutide Promoting Angiogenesis after Focal Cerebral Ischemia in Mice.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs administered before or after cerebral ischemia have been shown to provide neuroprotection. Here, we explored whether delayed administration of a GLP-1 analog, liraglutide, could improve long-term functional recovery and promote angiogenesis after stroke. MATERIALS AND METHODS: In the present study, mice were established as a focal cerebral cortical ischemia model and were intraperitoneally administered liraglutide or normal saline (NS) daily for 14 consecutive days, starting 1 day after cerebral ischemia. The neurological deficits were evaluated using rotarod test. The microvessel density (MVD) and endothelial cell (EC) proliferation were assessed by immunohistochemical staining. The expression of vascular endothelial growth factor (VEGF) was assessed by Western blot analysis. RESULTS: Liraglutide significantly reduced infarct volume and improved the rotarod test scores, compared with mice treated with NS. Liraglutide also greatly increased the MVD and EC proliferation and simultaneously upregulated the expression of VEGF in the cerebral ischemic area. CONCLUSIONS: These results demonstrated that liraglutide promoted angiogenesis and long-term recovery of cerebral ischemia through increasing the expression of VEGF.