Exosomal miR-370-3p increases the permeability of blood-brain barrier in ischemia/reperfusion stroke of brain by targeting MPK1

Ischemia/reperfusion (I/R) damage induced by stroke poses a serious hazard to human life, while mechanism of blood-brain barrier (BBB) dysfunction is still unknown. To imitate stroke induced ischemia conditions , the rat model of cerebral I/R damage was created by middle cerebral artery occlusion (M...

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Published in:Aging (Albany, NY.) NY.), 2023-03, Vol.15 (6), p.1931-1943
Main Authors: Gu, Caifeng, Mo, Weichun, Wang, Kunlun, Gao, Mingqiang, Chen, Junfeng, Zhang, Feng, Shen, Jie
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Blood-Brain Barrier - metabolism
Brain - metabolism
Brain Ischemia - genetics
Brain Ischemia - metabolism
Infarction, Middle Cerebral Artery - genetics
Ischemic Stroke - metabolism
MicroRNAs - genetics
MicroRNAs - metabolism
Rats
Reperfusion
Reperfusion Injury - genetics
Reperfusion Injury - metabolism
Research Paper
Stroke - genetics
Stroke - metabolism
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Summary:Ischemia/reperfusion (I/R) damage induced by stroke poses a serious hazard to human life, while mechanism of blood-brain barrier (BBB) dysfunction is still unknown. To imitate stroke induced ischemia conditions , the rat model of cerebral I/R damage was created by middle cerebral artery occlusion (MCAO). , the rat microvascular endothelial cell line bEND.3 was subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Evans blue was used to evaluate the permeability of the blood-brain barrier (BBB). To evaluate gene expression at the mRNA and protein levels, researchers used real-time PCR and western blotting. Infarct volume and BBB permeability were considerably higher in cerebral (I/R) animals than in the Sham group. Exosomal miR-370-3p expression was shown to be higher in the brains of I/R injured rats and OGD/R treatment bEND.3. The BBB permeability was considerably increased when miR-370-3p was downregulated in OGD/R pretreated bEND.3. miR-370-3p regulates MAPK1 expression by targeting it. In bEND.3, OGD/R therapy increased BBB permeability substantially. OGD/R was inhibited by miR-370-3p mimic transfection, while miR-370-3p mimic was abolished by co-transfection with MAPK1 overexpression lentivirus. In cerebral I/R damage, exosomal miR-370-3p targets MAPK1 and aggregates BBB permeability.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.204573