Dexmedetomidine inhibits inflammatory response and autophagy through the circLrp1b/miR-27a-3p/Dram2 pathway in a rat model of traumatic brain injury.

Abstract

Circular RNAs (circRNAs) have a regulatory function on inflammation and autophagy, of which rno-circRNA_010705 (circLrp1b) appears to be significantly up-regulated following traumatic brain injury (TBI). Dexmedetomidine (DEX) shows improvement effects in TBI by inhibiting NLRP3/caspase-1. However, whether circLrp1b plays critical roles in DEX-mediated TBI attenuation and the underlying mechanisms remain unclear. After TBI was established in rats by controlled cortical impact (CCI) to cause brain trauma, they received an intracerebroventricular injection of lentiviral vector, followed by intraperitoneal injection of DEX. Administration of DEX ameliorated autophagy in rats following TBI, accompanied by up-regulated circLrp1b and Dram2 and down-regulated miR-27a-3p. DEX promoted the effects of circLrp1b in attenuating TBI-induced neurologic impairment, autophagy, and inflammation, which was significantly reversed by inhibition of miR-27a-3p or Dram2 overexpression. Mechanistically, northern blot and luciferase reporter assays indicated that circLrp1b up-regulated Dram2 expression by functioning as a sponge for miR-27a-3p to promote autophagy involved in TBI, which was reversed by DEX treatment. Collectively, this study demonstrated that DEX inhibits inflammatory response and autophagy involved in TBI in vivo through inactivation of the circLrp1b/miR-27a-3p/Dram2 signaling pathway.