Microglial Autophagic Dysregulation in Traumatic Brain Injury: Molecular Insights and Therapeutic Avenues.

Abstract

Traumatic brain injury (TBI) is a complex and multifaceted condition that can result in cognitive and behavioral impairments. One aspect of TBI that has received increasing attention in recent years is the role of microglia, the brain-resident immune cells, in the pathophysiology of the injury. Specifically, increasing evidence suggests that dysfunction in microglial autophagy, the process by which cells degrade and recycle their own damaged components, may contribute to the development and progression of TBI-related impairments. Here, we unravel the pathways by which microglia autophagic dysregulation predisposes the brain to secondary damage and neurological deficits following TBI. An overview of the role of autophagic dysregulation in perpetuation and worsening of the inflammatory response, neuroinflammation, and neuronal cell death in TBI follows. Further, we have evaluated several signaling pathways and processes that contribute to autophagy dysfunction-mediated inflammation, neurodegeneration, and poor outcome in TBI. Additionally, a discussion on the small molecule therapeutics employed to modulate these pathways and mechanisms to treat TBI have been presented. However, additional research is required to fully understand the processes behind these underlying pathways and uncover potential therapeutic targets for restoring microglial autophagic failure in TBI.