Cited by 799Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury Research

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

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Jassam, Yasir N., Izzy, Saef, Whalen, Michael, McGavern, Dorian B., El Khoury, Joseph·2017·Neuron

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as "secondary injury." Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follow TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states toward a stimulus- and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

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Crossref · 10.1016/j.neuron.2017.07.010

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  • This alarmin detection triggers a rapid inflammatory response characterized by inflammasome assembly, nuclear factor-κβ signaling, resident immune cell activation, cytokine and chemokine production, and recruitment of peripheral myelomonocytic cells.

    “This, in turn, triggers a rapid inflammatory response characterized by inflammasome assembly, nuclear factor-κβ signaling, resident immune cell activation, cytokine and chemokine production (such as IL-6, TNFα, CXCL1, CXCL2, and CCL2), and recruitment of peripheral myelomonocytic cells, among others (Fig. 4) (130).”
  • TBI and associated CNS vascular damage is a type of sterile injury.

    “TBI and the associated CNS vascular damage is a type of sterile injury [recently reviewed in (130)].”

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Authors
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J.
Affiliations
  • National Institutes of Health (US)
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
Corresponding author
McGavern, Dorian B.
Venue
Neuron
Publisher
Elsevier BV
Published
2017-09
Volume
95
Issue
6
Pages
1246-1265
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2754554955
Cited by
799
References
270
Citations by year
2026: 76 · 2025: 87 · 2024: 83 · 2023: 99 · 2022: 130 · 2021: 124 · 2020: 96 · 2019: 62 · 2018: 39 · 2017: 3
FWCI
7.33
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH
  • NIA (RF1AG051506)
  • NINDS (1R21HD086385)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, neuroimmunology, neuroinflammation, secondary injury, innate immunity, adaptive immunity, immune cell polarization, gene expression profiling, proteomic profiling, immune signaling pathways, immunomodulatory therapy
MeSH terms
Brain Injuries, Traumatic, Animals, Astrocytes, Humans, Immunity, Innate, Inflammation, Microglia, Models, Immunological, Proteomics, Adaptive Immunity, Transcriptome

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