神经损伤与功能重建2025，Vol.20Issue(5)：后插1-后插1,1.DOI:10.16780/j.cnki.sjssgncj.202505015
脊髓损伤后不同时间点小胶质细胞IKKβ改变中枢和外周免疫活性
Microglial IKKβ Alters Central and Peripheral Immune Activity at Distinct Time Points After Spinal Cord Injury
Micaela L O'Reilly 1王晶 1Mariah J Wulf 1Theresa M Connors 1Ying Jin 1Frank Bearoff 1Julien Bouyer 1Sandhya Kortagere 1John R Bethea 1Veronica J Tom1
作者信息
摘要
Abstract
After high-level spinal cord injury(SCI),persistently reactive microglia drive widespread plasticity through-out the neuraxis.Plasticity in the thoracolumbar cord,a region corresponding to the spinal sympathetic reflex(SSR)cir-cuit,contributes to the development of sympathetic dysfunction and associated immune disorders.The transcription fac-tor NF-κB is activated after SCI,promoting a pro-inflammatory loop by driving the expression of inflammatory media-tors which further activate NF-κB signaling.We hypothesize that microglial NF-κB signaling via IKKβ modulates mi-croglial activity,impacting central and peripheral immune activity related to the SSR circuit post-SCI.We assessed the effect of deleting canonical IKKβ in CNS-resident microglia,its impact on microglial activation,polarization,central transcriptional activity,and peripheral immune activity at 1-and 4-week post-SCI(wpi).Transcriptomic analyses reveal microglial IKKβ influences immune-related pathways in the thoracolumbar cord at 1 wpi.We show that inhibition of mi-croglial NF-κB signaling via deletion of the activator IKKβ mitigates injury-induced increases in"proinflammatory"M1 microglia in the thoracolumbar cord at 4 wpi and increases the quantity of splenocytes at 1 wpi.This study advances our understanding of how microglial IKKβ signaling shapes the neuroimmune response and a peripheral immune organ after SCI.关键词
IKKβ/NF-κB/Tmem119/小胶质细胞/脊髓损伤Key words
IKKβ/NF-κB/Tmem1 19/microglia/spinal cord injury分类
临床医学引用本文复制引用
Micaela L O'Reilly,王晶,Mariah J Wulf,Theresa M Connors,Ying Jin,Frank Bearoff,Julien Bouyer,Sandhya Kortagere,John R Bethea,Veronica J Tom..脊髓损伤后不同时间点小胶质细胞IKKβ改变中枢和外周免疫活性[J].神经损伤与功能重建,2025,20(5):后插1-后插1,1.
