Inflammation in Traumatic Brain Injury

Article type: Review Article

Authors: Postolache, Teodor T.^{a; b; c; d; *} | Wadhawan, Abhishek^{a; e} | Can, Adem^f | Lowry, Christopher A.^{b; c; g; h} | Woodbury, Margaret^{a; i} | Makkar, Hina^a | Hoisington, Andrew J.^{b; j} | Scott, Alison J.^k | Potocki, Eileenⁱ | Benros, Michael E.^l | Stiller, John W.^{a; m; n}

Affiliations: [a] Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA | [b] Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Aurora, CO, USA | [c] Military and Veteran Microbiome: Consortium for Research and Education (MVM-CoRE), Aurora, CO, USA | [d] Mental Illness Research, Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 5, VA Capitol Health Care Network, Baltimore, MD, USA | [e] Saint Elizabeths Hospital, Department of Psychiatry, Washington, DC, USA | [f] School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA | [g] Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA | [h] Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO, USA | [i] VA Maryland Healthcare System, Baltimore VA Medical Center, Baltimore, MD, USA | [j] Systems Engineering and Management, Air Force Institute of Technology, Wright-Patterson AFB, OH, USA | [k] Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA | [l] Copenhagen Research Center for Mental Health-CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark | [m] Maryland State Athletic Commission, Baltimore, MD, USA | [n] Saint Elizabeths Hospital, Neurology Consultation Services, Washington, DC, USA

Correspondence: [*] Correspondence to: Teodor T. Postolache, MD, 685 W. Baltimore Street, MSTF Building, Suite # 930, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Tel.: +1 410 706 2323; E-mail: tpostola@som.umaryland.edu.

Abstract: There is an increasing evidence that inflammation contributes to clinical and functional outcomes in traumatic brain injury (TBI). Many successful target-engaging, lesion-reducing, symptom-alleviating, and function-improving interventions in animal models of TBI have failed to show efficacy in clinical trials. Timing and immunological context are paramount for the direction, quality, and intensity of immune responses to TBI and the resulting neuroanatomical, clinical, and functional course. We present components of the immune system implicated in TBI, potential immune targets, and target-engaging interventions. The main objective of our article is to point toward modifiable molecular and cellular mechanisms that may modify the outcomes in TBI, and contribute to increasing the translational value of interventions that have been identified in animal models of TBI.

Keywords: Depression, glia, immune challenge, immunomodulation, inflammation, priming, probiotic, traumatic brain injury

DOI: 10.3233/JAD-191150

Journal: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 1-28, 2020