Up-regulation of circARF3 reduces blood-brain barrier damage in rat subarachnoid hemorrhage model via miR-31-5p/MyD88/NF-κB axis.

ABSTRACT: Inflammation events have been found to aggravate brain injury and blood-brain barrier (BBB) damage following subarachnoid hemorrhage (SAH). This study probed the role and mechanism of a novel circRNA, circARF3, in regulating the BBB injury in SAH rats and hypoxia-induced vascular endothelial cell (VEC) injury in vitro. Levels of circARF3 and miR-31-5p were monitored by RT-PCR. The expression of inflammatory factors IL-1β and TNF-α was verified by ELISA. In vivo SAH model was constructed in Sprague Dawley (SD) rats. The BBB integrity and cerebral edema, as well as the neurological functions of the rats were evaluated. The apoptotic neurons and microglia in brain lesions were examined by immunohistochemistry (IHC). The MyD88/NF-κB pathway was tested by Western blot. Furthermore, gain-of functional assay were constructed to explore the effects of circARF3 and miR-31-5p in primary cultured brain microvascular endothelial cell (BMEC) injury and microglial inflammation induced by oxygen and glucose deprivation (OGD). circARF3 was significantly down-regulated in plasma and CSF in SAH patients with higher Fisher stages. In the SAH rat model, overexpressing circARF3 improved BBB integrity and neurological score, decreased neuronal apoptosis and microglial activation in ipsilateral basal cortex, with declined miR-31-5p expression and MyD88-NF-κB activation. In vitro, overexpressing circARF3 attenuated OGD-mediated integrity destruction of BMECs and microglial induced neuroinflammation, while overexpressing miR-31-5p had opposite effects. Mechanistically, circARF3 sponged miR-31-5p as an endogenous competitive RNA and dampens its expression, thus inactivating MyD88-NF-κB pathway. CircARF3 attenuates BBB destruction in SAH rats by regulating the miR-31-5p-activated MyD88-NF-κB pathway.

SUBMITTER: Cai L 

PROVIDER: S-EPMC8457610 | biostudies-literature |

REPOSITORIES: biostudies-literature