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

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.