Overview of Traumatic Brain Injury: An Immunological Context

Abstract

Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated with TBIs and for the chronic neuropathological and neurobehavioral deficits. Inflammation and neuroinflammation appear to be major mediators of TBI outcomes. These systems are being intensively studies using animal models and human translational studies, in the hopes of understanding the mechanisms of TBI, and developing therapeutic strategies to improve the outcomes of the millions of people impacted by TBIs each year. This manuscript provides an overview of the epidemiology and outcomes of TBI, and presents data obtained from animal and human studies focusing on an inflammatory and immunological context. Such a context is timely, as recent studies blur the traditional understanding of an “immune-privileged” central nervous system. In presenting the evidence for specific, adaptive immune response after TBI, it is hoped that future studies will be interpreted using a broader perspective that includes the contributions of the peripheral immune system, to central nervous system disorders, notably TBI and post-traumatic syndromes.

Innate immune responses to trauma

“…When exposed to DAMPs, phagocytic microglia are rapidly activated to clear debris (for example, a hematoma), seal defective barriers and produce neurotrophic factors 105–107 . However, microglia are also critical for an extensive and often sustainable (up to years) generation of cytokines (for example, IL-1β and IL-6) and ROS, which in turn recruit neutrophils and blood monocytes-macrophages to the injured area 103,105,108 . Furthermore, complement 109 or lysophosphatidylcholine activates inflammasomes in microglia or astrocytes soon after TBI and during neuro-inflammation 110 .…”

Hydrogen sulfide therapy in brain diseases: from bench to bedside

“…TBI is defined as a serious public health problem that disrupts the normal function of the brain and can be caused by a bump, blow or jolt to the head, rapid acceleration and deceleration of the calvarium, or a penetrating head injury 37. There are certain experiments have shown that TBI usually led to brain edema, tissue loss, neurocognitive impairments, and dysfunction of the CNS 38.…”

Greater neurodegeneration and behavioral deficits after single closed head traumatic brain injury in adolescent vs adult mice

“…Previous studies have shown that delayed injury is consistently marked by microglial activation and is mediated by inflammatory processes after TBI. 25,26,27 Behaviorally, adolescent TBI animals had lower locomotor velocity shortly after TBI and were no longer distinguishable from controls by 16 DPI. Both adult and adolescent sham and TBI animals increased center time from 4 DPI to 16 DPI.…”