Unraveling the complexity of microglial responses in traumatic brain and spinal cord injury.

Microglia, the resident innate immune cells of the central nervous system (CNS), play an important role in neuroimmune signaling, neuroprotection, and neuroinflammation. In the healthy CNS, microglia adopt a surveillant and antiinflammatory phenotype characterized by a ramified scanning morphology that maintains CNS homeostasis. In response to acquired insults, such as traumatic brain injury (TBI) or spinal cord injury (SCI), microglia undergo a dramatic morphologic and functional switch to that of a reactive state. This microglial switch is initially protective and supports the return of the injured tissue to a physiologic homeostatic state. However, there is now a significant body of evidence that both TBI and SCI can result in a chronic state of microglial activation, which contributes to neurodegeneration and impairments in long-term neurologic outcomes in humans and animal models. In this review, we discuss the complex role of microglia in the pathophysiology of TBI and SCI, and recent advancements in knowledge of microglial phenotypic states in the injured CNS. Furthermore, we highlight novel therapeutic strategies targeting chronic microglial responses in experimental models and discuss how they may ultimately be translated to the clinic for human brain and SCI.