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

Abstract:

: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.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Xiao ZH,Wang L,Gan P,He J,Yan BC,Ding LD

doi

10.1007/s11064-020-02986-4

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

1107-1119

issue

5

eissn

0364-3190

issn

1573-6903

pii

10.1007/s11064-020-02986-4

journal_volume

45

pub_type

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