Dynamic Changes in miR-126 Expression in the Hippocampus and Penumbra Following Experimental Transient Global and Focal Cerebral Ischemia–Reperfusion

• Published in: Neurochemical research Vol. 45; no. 5; pp. 1107 - 1119
• Main Authors: Xiao, Zhang Hong, Wang, Li, Gan, Ping, He, Jing, Yan, Bing Chun, Ding, Li Dong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2020; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - genetics; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Biology; Cell death; Cell viability; Deprivation; Endothelial cells; Gene Expression; Gerbillinae; Glial cells; Growth factors; Hippocampus - metabolism; Hippocampus - pathology; Ischemia; Ischemic Attack, Transient - genetics; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Male; Mice; Mice, Inbred ICR; MicroRNAs - biosynthesis; MicroRNAs - genetics; Neurochemistry; Neurology; Neuronal-glial interactions; Neuroprotection; Neurosciences; Original Paper; PC12 Cells; Pheochromocytoma cells; Rats; Reperfusion; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Statistical analysis; Vascular endothelial growth factor; VEGFA/SPRED1/ raf-1 signaling pathway; Cerebral ischemia; Neuronal damage; Vascular; miR-126
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-020-02986-4

miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia–reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how miR-126 changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism miR-126 involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of miR-126-3p and miR-126-5p expression in mice and gerbils after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of miR-126-3p exacerbated the OGD/R-induced cell death and reduced cell viability. After miR-126-3p inhibition, the levels of SPRED1 and VEGFA expression were increased, and p -Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of miR-126-3p inhibition, we found that the expression of p -Raf-1 was significantly increased after the intervention of siSPRED1 , while it was not statistically significant after intervention of siVEGFA . The reduction of miR-126 expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.