Neuroimmune cleanup crews in brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability. Mounting evidence indicates that the immune system is critically involved in TBI pathogenesis, where it is deployed to dispose of neurotoxic material generated from head trauma and to instruct the wound healing process. However, the immune response to brain damage must be carefully held in check as aberrant regulation of immune signaling can lead to deleterious neuroinflammation, brain pathology, and neurological dysfunction. Efficient clearance of neurotoxic material by microglia (the brain's resident phagocytes) and the glymphatic-meningeal lymphatic drainage system are paramount to keeping the immune system in balance following head trauma. In this review, we highlight emerging evidence that defines pivotal roles for microglia and the recently discovered glymphatic-meningeal lymphatic system in TBI pathogenesis.