Beyond the Impact: Decoding the Inflammatory Cascade in Traumatic Brain Injury
Abstract:
Traumatic brain injury (TBI) is a large-scale health issue which reports high levels of long-term disability and death. Beyond the initial mechanical damage TBI sets in motion a series of secondary injury processes in which neuroinflammation is very much at the core. In this review we look at the patho-physiological processes which follow TBI with a close look at glial cell action, inflammasome signaling, and the chronic inflammatory environ ment which play a role in the development of long-term neurodegeneration. After TBI the blood barrier breaks down which in turn allows for peripheral immune cells to enter the central nervous system. Resident microglia and astrocytes become activated which in turn produce a range of pro in f lammatory cytokines and reactive oxygen species. This immune response which is at first protective can become dysregulated and may persist over time thus contributing to ongoing neuronal damage and synaptic dysfunction. In the center of this response are inflammasomes which are the NLRP3 inflammasome that play a role in the maturation and release of key pro inflammatory cytokines like IL-1beta and IL-18. Chronic neuroinflammation in the wake of TBI is reported to play a large role in progressive cognitive decline and in the increase of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. We present a review of present research related to the cell and molecular bases of inflammation post TBI which also puts into focus the roles of microglia, astrocytes, inflammasomes, and systemic immune responses. These we have as a base which is then used to put forth new therapeutic approaches which in turn will improve the long-term effects of TBI. We see in chronic neuroinflammation a very promising area for intervention to better the health outcomes in TBI patients and to also in turn reduce the social impact of what is a very complex and at time disabling condition.
