GluR1 protects hypoxic ischemic brain damage via activating Akt signaling pathway in neonatal rats

OBJECTIVE: To investigate the role of glutamic acid receptor 1 (GluR1) in hypoxic-ischemic brain damage (HIBD) in neonatal rats and its underlying mechanism.

MATERIALS AND METHODS: 7-day-old neonatal rats received right common carotid artery (CCA) ligation for the establishment of HIBD. After the operation, rats were sacrificed at different time points (0, 4, 6, 12, 24, 48, and 72 h), respectively. Meanwhile, rats in Sham group underwent similar procedures without ligation. Lentivirus-GLUR1-shRNA (LV-GLUR1 shRNA group) was constructed and then transfected into the right lateral ventricles of rats to inhibit GluR1 in vivo. Rats received LV-control injection were selected in the control group (LV-control group). After injection of Lentivirus-GLUR1-shRNA, CCA ligation was performed in rats for HIBD construction. Western blot was performed to detect the protein levels of GLUR1, Akt, p-Akt, and vascular endothelial growth factor (VEGF) in brain tissues. Cell apoptosis was measured by TUNEL staining assay.

RESULTS: After hypoxic ischemia (HI), GLUR1 expression increased gradually and reached a peak at 24 h. Meanwhile, p-Akt expression increased immediately and then gradually decreased. 24 h later, p-Akt expression increased again and peaked at 48 h. VEGF expression increased at 4 h after HI and reached a peak at 12 h. The expression levels of GLUR1, p-Akt, and VEGF in the brain tissues derived from rats transfected with LV-GLUR1 shRNA significantly decreased at both 4 h and 24 h after HI. In addition, results indicated that cell apoptosis was enhanced after LV-GLUR1 shRNA administration, suggesting the role of GLUR1 in protecting against HIBD.

CONCLUSIONS: GLUR1 exhibits a remarkable protective role in HIBD, which may be related to the activation of the Akt signaling pathway and the upregulation of VEGF after HI.

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