miR-499-5p suppresses C-reactive protein and provides neuroprotection in hypoxic-ischemic encephalopathy in neonatal rat.

Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and permanent neurologic deficit. Recent data suggested microRNAs (miRNAs) may have essential functions in the regulation of HIE. This study aims to investigate the functional role of miR-499-5p and the underlying mechanism in regulating neonatal hypoxia-ischemia (HI)-induced brain injury. Dual-luciferase reporter assay and western blotting assay were performed to investigate the relationship between miR-499-5p and C-reactive protein (CRP). TUNEL staining assay was applied to evaluate neuronal cell apoptosis in the hippocampus after administration of miR-499-5p in HIE rat model. Neurobehavioral assays were conducted to evaluate the effect of miR-499-5p on the neurological functions of rat pups with HI-induced brain injury. Our study showed that miR-499-5p regulated CRP expression in L-02 cells and rat HIE model. The miR-499-5p treatment resulted in significant reduction of neuronal cell apoptosis and the infarct size of the brain. Furthermore, administration of miR-499-5p significantly improved spatial learning ability, spatial memory, and locomotor function of rat pups with HIE. Our data demonstrated that miR-499-5p have a neuroprotective effect in HI-induced brain injury in rat pups, which suggests a potential therapeutic application of miR-499-5p in the treatment of neonatal HIE.