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The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments

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Abstract

This review recounts the definitions and research evidence supporting the multifaceted roles of neuroinflammation in the injured brain following trauma. We summarise the literature fluctuating from the protective and detrimental properties that cytokines, leukocytes and glial cells play in the acute and chronic stages of TBI, including the intrinsic factors that influence cytokine responses and microglial functions relative to genetics, sex, and age. We elaborate on the pros and cons that cytokines, chemokines, and microglia play in brain repair, specifically neurogenesis, and how such conflicting roles may be harnessed therapeutically to sustain the survival of new neurons. With a brief review of the clinical and experimental findings demonstrating early and chronic inflammation impacts on outcomes, we focus on the clinical conditions that may be amplified by neuroinflammation, ranging from acute seizures to chronic epilepsy, neuroendocrine dysfunction, dementia, depression, post-traumatic stress disorder and chronic traumatic encephalopathy. Finally, we provide an overview of the therapeutic agents that have been tested to reduce inflammation-driven secondary pathological cascades and speculate the future promise of alternative drugs.

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Acknowledgements

BDS is supported by a NHMRC Career Development Fellowship and the Central Clinical School, Monash University at the Alfred Hospital. Figure 3 provided by P. Casillas-Espinosa, W.L. Leung and L. Dill, Monash University.

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Authors and Affiliations

  1. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Maria Cristina Morganti-Kossmann

  2. Australian New Zealand Intensive Care Research Centre, Melbourne, VIC, Australia

    Maria Cristina Morganti-Kossmann

  3. Department of Neuroscience, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, VIC, Australia

    Bridgette D. Semple

  4. Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia

    Bridgette D. Semple

  5. Sydney Translational Imaging Laboratory, Charles Perkins Centre, Heart Research Institute, University of Sydney, Sydney, NSW, Australia

    Sarah C. Hellewell

  6. Department of Pharmacy, College of Health and Medicine, University of Tasmania, Sandy Bay, TAS, Australia

    Nicole Bye

  7. Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia

    Jenna M. Ziebell

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  1. Maria Cristina Morganti-Kossmann
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Correspondence to Maria Cristina Morganti-Kossmann.

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Morganti-Kossmann, M.C., Semple, B.D., Hellewell, S.C. et al. The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments. Acta Neuropathol 137, 731–755 (2019). https://doi.org/10.1007/s00401-018-1944-6

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