NF-κB activation in astrocytes impairs wound healing after traumatic brain injury in male mice

TL;DR

NF-κB activation in astrocytes after brain injury in male mice worsens recovery by disrupting healing processes.

Contribution

The study identifies NF-κB activation in astrocytes as a harmful mechanism impairing CNS wound healing after TBI.

Findings

NF-κB activation in astrocytes disrupts their homeostatic functions after TBI.

It amplifies neuroimmune responses and hinders CNS scar development.

Paracrine signaling from NF-κB-activated astrocytes prevents CNS restoration.

Abstract

Traumatic brain injury (TBI) is a complex condition in which multiple pathophysiological mechanisms influence the course of the disease. After the initial mechanical impact, neuroinflammatory reactions of glial cells along with infiltrating peripheral immune cells determine the overall clinical outcome. However, these secondary processes and their molecular determinants promoting either beneficial or detrimental consequences are not well-defined. Here, we show that TBI-mediated NF-κB activation in astrocytes impairs their homeostatic functions, amplifies the post-traumatic neuroimmune response and disturbs the multicellular CNS scar development in a male mouse model of TBI. Our results further demonstrate a specific deficit in the formation of the glial limitans border and establish that paracrine signaling pathways induced by NF-κB-activated astrocytes can prevent a beneficial restoration of the CNS integrity after TBI. These findings enhance our understanding on the NF-κB-mediated post-traumatic pathophysiology and provide information on future targeted therapies to improve TBI outcome.

The secondary neuroinflammatory immune response determines the overall clinical outcome after traumatic brain injury (TBI). Here, the authors show in a mouse TBI model that NF-kB activation in astrocytes is a pathological mechanism limiting beneficial CNS wound healing.

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