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Microglial IKKβ Alters Central and Peripheral Immune Activity at Distinct Time Points After Spinal Cord Injury
Journal article   Peer reviewed

Microglial IKKβ Alters Central and Peripheral Immune Activity at Distinct Time Points After Spinal Cord Injury

Micaela L O'Reilly, Mariah J Wulf, Theresa M Connors, Ying Jin, Frank Bearoff, Julien Bouyer, Sandhya Kortagere, John R Bethea and Veronica J Tom
Glia, v 73(8), pp 1746-1766
Aug 2025
DOI: https://doi.org/10.1002/glia.70030
PMID: 40346894
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1002/glia.70030View
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Abstract

IKK beta microglia NF-kappa B Tmem119 Spinal Cord Injury
After high-level spinal cord injury (SCI), persistently reactive microglia drive widespread plasticity throughout the neuraxis. Plasticity in the thoracolumbar cord, a region corresponding to the spinal sympathetic reflex (SSR) circuit, contributes to the development of sympathetic dysfunction and associated immune disorders. The transcription factor NF-κB is activated after SCI, promoting a pro-inflammatory loop by driving the expression of inflammatory mediators which further activate NF-κB signaling. We hypothesize that microglial NF-κB signaling via IKKβ modulates microglial 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 microglial 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.After high-level spinal cord injury (SCI), persistently reactive microglia drive widespread plasticity throughout the neuraxis. Plasticity in the thoracolumbar cord, a region corresponding to the spinal sympathetic reflex (SSR) circuit, contributes to the development of sympathetic dysfunction and associated immune disorders. The transcription factor NF-κB is activated after SCI, promoting a pro-inflammatory loop by driving the expression of inflammatory mediators which further activate NF-κB signaling. We hypothesize that microglial NF-κB signaling via IKKβ modulates microglial 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 microglial 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.

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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