Biomarkers of Brain Cell-Specific Immune Mechanisms and Their Translational Potential: State of the Evidence for Traumatic Brain Injury

Abstract This review summarizes the immune mechanisms involved in traumatic brain injury (TBI), with a particular focus on the involvement of microglia and astrocytes. Both innate and adaptive immune responses contribute to secondary neuroinflammation-mediated damage following TBI. Microglia, which interact closely with neurons to maintain brain homeostasis, become activated in response to injury, in particular, due to signals from damaged neurons and other immune cells. Astrocytes, essential for normal functioning of the central nervous system (CNS), are also involved in neuroinflammatory processes in brain diseases. While microglia are the primary source of innate immunity in the brain, astrocytes and peripheral immune cells, including adaptive and innate components, also play critical roles in the neuroinflammatory response. Glial contribution to neuroinflammation in experimental TBI and the involvement of the immune system in post-traumatic neurodegeneration are discussed. A key area of current research is understanding the biochemical changes caused by TBI for clinical implications and novel therapeutic strategies. Microglia show particular promise as targets for developing new TBI biomarkers and treatment strategies. Clinical biomarkers of TBI include biomarkers of microglial activation and astrocytic damage as well as other markers not specific to microglial or astroglial cells (biomarkers of inflammation, neuronal damage, oligodendroglial damage, tau protein accumulation). Currently, most available clinical biomarkers of TBI lack specificity, as they reflect general inflammatory or neurodegenerative processes involving neurons, astrocytes, oligodendrocytes or even having an extra-brain source