circCrebrf modulates the miR-3562/ERLIN1 axis to suppress neuronal oxidative stress and apoptosis following traumatic brain injury.

Traumatic brain injury (TBI) is a life-threatening medical emergency that can induce a variety of neurological disorders. Circular RNAs (circRNAs) play critical roles in neural development, maintenance of homeostasis, and the pathogenesis of neurological disorders. Nevertheless, the precise role of circRNAs in TBI remains unclear. In this study, we found that the expression level of circular RNA Crebrf (circCrebrf) was significantly downregulated in the cerebral cortex of rats following traumatic brain injury (TBI), and it was abundantly expressed in neurons. Furthermore, overexpression of circCrebrf could significantly ameliorate TBI-induced neurological deficits, cognitive impairment and neuronal apoptosis. Mechanistic investigations revealed that circCrebrf acted as a molecular sponge by specifically adsorbing miR-3562, thereby upregulating endoplasmic reticulum lipid-anchoring protein 1 (ERLIN1) expression. In turn, the upregulation of ERLIN1 effectively ameliorated mitochondrial dysfunction and suppressed cell apoptosis. Taken together, circCrebrf exerts a neuroprotective effect by regulating the miR-3562/ERLIN1 axis, thus alleviating secondary neurological injury following TBI. Therefore, circCrebrf is a promising novel potential therapeutic target for TBI intervention.