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  • LncRNA SNHG8 sponges miR-449c-5p and regulates the SIRT1/FoxO1 pathway to affect microglia activation and blood-brain barrier permeability in ischemic stroke.

LncRNA SNHG8 sponges miR-449c-5p and regulates the SIRT1/FoxO1 pathway to affect microglia activation and blood-brain barrier permeability in ischemic stroke.

Journal of leukocyte biology (2021-09-30)
Duobin Zhang, Ning Pan, Chuan Jiang, Maolin Hao
RESUMO

Ischemic stroke (IS) can cause disability and death, and microglia as the immune component of the CNS can release inflammatory factors and participate in blood-brain barrier (BBB) dysfunction. This study aimed to investigate the effects of long noncoding RNA (lncRNA) SNHG8 on microglia activation and BBB permeability in IS. A rat model of permanent middle cerebral artery occlusion (p-MCAO) and a cell model of oxygen and glucose deprivation (OGD) in microglia were established, followed by evaluation of neurobehavioral function, BBB permeability, brain edema, and pathologic changes of microglia in brain tissue. The activation status of microglia and expressions of inflammatory factors were detected. Cell viability and integrity of microglia membrane were assessed. The downstream microRNA (miR), gene, and pathway of SNHG8 were analyzed. LncRNA SNHG8 was down-regulated in MCAO rats. Overexpression of SNHG8 improved the neural function defect, reduced brain water content, BBB permeability, brain tissue damage and inflammation, and inhibited microglia activation. In OGD-induced microglia, overexpression of SNHG8 or miR-449c-5p down-regulation increased cell viability and decreased lactate dehydrogenase activity. Moreover, SNHG8 sponged miR-449c-5p to regulate SIRT1. Overexpression of SNHG8 increased the expression of SIRT1 and FoxO1. MiR-449c-5p mimic could annul the effect of SNHG8 overexpression on ischemic microglia. Collectively, SNHG8 inhibits microglia activation and BBB permeability via the miR-449c-5p/SIRT1/FoxO1 pathway, thus eliciting protective effects on ischemic brain injury.

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