Role of innate inflammation in traumatic brain injury

Abstract

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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Abbreviations

AP-1:

activator protein 1

ATP:

adenosine triphosphate

BBB:

blood-brain barrier

BDNF:

brain-derived neurotrophic factor

CNS:

central nervous system

CSF:

cerebrospinal fluid

CSF1R:

colony stimulating factor 1 receptor

DAI:

diffuse axonal injury

DAMPs:

danger-associated molecular patterns

EPO:

erythropoietin

GCS:

Glasgow Coma Scale

GFAP:

glial fibrillary acidic protein

GR:

glucocorticoid receptors

ICP:

intracranial pressure

IL-1:

interleukin-1

IL-1R1:

IL-1 receptor type 1

IL-1Ra:

IL-1R antagonist protein

MAPK:

mitogen-activated protein kinase

MMP-9:

matrix metalloproteinase-9

Mtran:

mixed translational

NF:

neurofilament protein.

NF-κB:

nuclear factor-κB

NLRP3:

NLR family pyrin domain containing 3

NSE:

neuron-specific enolase

NVU:

neurovascular unit

PRRs:

pattern recognition receptors

ROS:

reactive oxygen species

SHH:

Sonic Hedgehog protein

TBI:

traumatic brain injury

TLRs:

toll-like receptors

TNF-α:

tumor necrosis factor alpha

UCHL1:

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.

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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). https://doi.org/10.1007/s10072-020-05002-3

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Keywords

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