Role of innate inflammation in traumatic brain injury


Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective neuroprotective strategy. Following brain trauma, secondary injury from molecular, metabolic, and cellular changes causes progressive cerebral tissue damage. Chronic neuroinflammation following traumatic brain injuries is a key player in the development of secondary injury. Targeting this phenomenon for development of effective neuroprotective therapies holds promise. This strategy warrants a concrete understanding of complex neuroinflammatory mechanisms. In this review, we discuss pathophysiological mechanisms such as the innate immune response, glial activation, blood-brain barrier disruption, activation of immune mediators, as well as biological markers of traumatic brain injury. We then review existing and emerging pharmacological therapies that target neuroinflammation to improve functional outcome.

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activator protein 1


adenosine triphosphate


blood-brain barrier


brain-derived neurotrophic factor


central nervous system


cerebrospinal fluid


colony stimulating factor 1 receptor


diffuse axonal injury


danger-associated molecular patterns




Glasgow Coma Scale


glial fibrillary acidic protein


glucocorticoid receptors


intracranial pressure




IL-1 receptor type 1


IL-1R antagonist protein


mitogen-activated protein kinase


matrix metalloproteinase-9


mixed translational


neurofilament protein.


nuclear factor-κB


NLR family pyrin domain containing 3


neuron-specific enolase


neurovascular unit


pattern recognition receptors


reactive oxygen species


Sonic Hedgehog protein


traumatic brain injury


toll-like receptors


tumor necrosis factor alpha


ubiquitin C-terminal hydrolase-L1


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AW and SC originated the idea of the article.

SBT drafted the initial manuscript, performed the literature search, and revised the manuscript.

AW, SC, J-CR, and LBD assisted in the preparation of the manuscript, substantively revised the work, and approved the submitted version.

All authors have approved the final manuscript as submitted and agree to be personally accountable all aspects of the review.

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Correspondence to Alexander G Weil.

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Bourgeois-Tardif, S., De Beaumont, L., Rivera, J.C. et al. Role of innate inflammation in traumatic brain injury. Neurol Sci (2021).

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  • Traumatic brain injury
  • Neuroinflammation
  • Microglia
  • Blood-brain barrier
  • Cytokine
  • Innate inflammation