Overexpressing circ_0000831 is sufficient to inhibit neuroinflammation and vertigo in cerebral ischemia through a miR-16-5p-dependent mechanism

Circular RNAs (circRNAs) hold potential as stroke-related biomarkers due to involvement in various pathophysiological processes associated with cerebral ischemia and stability in peripheral blood. Differentially expressed circulating circRNAs were identified by preliminary sequencing analysis, through which we identified underexpressed circ_0000831 in ischemic stroke (IS). Validation was performed in peripheral blood of IS patients by quantitative polymerase chain reaction. Microglia was exposed to oxygen-glucose deprivation (OGD), where polarization phenotypes and inflammation were assessed. Middle cerebral artery occlusion was performed in mice to mimic ischemic stroke-induced vertigo, where cerebral blood flow, neurological deficits, vertigo degree, infarct area, inflammation and cell apoptosis were assayed in response to ectopic expression and knockdown of circ_0000831, miR-16-5p, and AdipoR2. Mechanically, circ_0000831 bound to miR-16-5p and downregulated miR-16-5p, and AdipoR2 was targeted by miR-16-5p and increased PPARγ expression in microglia. Furthermore, circ_0000831, AdipoR2, or PPARγ overexpression or miR-16-5p inhibition alleviated neuroinflammation, vertigo, neurological deficit, and cell apoptosis in MCAO mice. Consistently, circ_0000831, AdipoR2, or PPARγ upregulation or miR-16-5p downregulation diminished apoptosis and inflammation of OGD-induced microglia. Consequently, these findings pinpoint the circ_0000831/miR-16-5p/AdipoR2 axis as an essential signaling pathway during ischemia stroke. Thus, the circRNA circ_0000831 may work as a possible target for novel treatment in patients with ischemic stroke.