HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury

Long noncoding RNAs(lnc RNAs)participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis.Homeobox A11 antisense RNA(HOXA11-AS)is a member of the lnc RNA family that has been reported to participate in many inflammatory reactions;however,its role in traumatic brain injury remains unclear.In this study,we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling.The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats,increased brain edema and apoptosis,promoted the secretion of proinflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factorα,and promoted the activation of astrocytes and microglia.Microglia were treated with 100 ng/m L lipopolysaccharide for 24 hours to establish in vitro cell models,and then transfected with pc DNA-HOXA11-AS,mi R-124-3 p mimic,or sh-MDK.The results revealed that HOXA11-AS inhibited mi R-124-3 p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation.Furthermore,lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes.Forced overexpression of mi R-124-3 p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes.However,the mi R-124-3 p-mediated anti-inflammatory effects were reversed by HOXA11-AS.These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the mi R-124-3 p-MDK axis.This study was approved by the Animal Protection and Use Committee of Southwest Medical University(approval No.SMU-2019-042)on February 4,2019.