Background: Subarachnoid hemorrhage (SAH) is a severe acute neurological disorder. SAH causes neuroinflammation and leads to early brain injury (EBI) and secondary injury. MicroRNAs are crucial regulators in a variety of neurological diseases. This study was performed to decipher how miR-340-5p functions in SAH.
Methods: An experimental mouse model with SAH was established by the intravascular perforation, and the in vitro SAH model was constructed by exposing cocultured primary neurons and microglia to oxyhemoglobin. After overexpression of miR-340-5p in mice, the neurobehavioral disorders were evaluated by Garcia test; brain edema was evaluated by wet-dry method; blood-brain barrier (BBB) damage was detected with Evan's blue staining; levels of inflammatory cytokines were detected with enzyme-linked immunosorbent assay. After miR-340-5p was transfected in to microglia, Iba-1 expression was detected by Western blot, and neuronal apoptosis were detected with flow cytometry. The targeting relationship between miR-340-5p and STING was verified by dual-luciferase reporter gene assay and RNA immunoprecipitation assay.
Results: MiR-340-5p was significantly inhibited in the brain tissues of mice with SAH and microglia of SAH model, and neurological impairment, brain edema, BBB injury, and neuroinflammation were significantly alleviated in mice after overexpressing miR-340-5p. STING was identified as a target of miR-340-5p, and STING overexpression could counteract the effects of miR-340-5p overexpression on neurons.
Conclusion: MiR-340-5p can attenuate EBI caused by SAH-induced neuroinflammation by inhibiting STING.
Keywords: STING; early brain injury; miR-340-5p; neuroinflammation; subarachnoid hemorrhage.
© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.