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Cited by 27Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchNeuroinflammation and Neurodegeneration Mechanisms

Temporal patterns of microglial activation in white matter following experimental mild traumatic brain injury: A systematic literature review

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Velayudhan, Prashanth S., Schwab, Nicole, Hazrati, Lili-Naz, Wheeler, Anne L.·2021·Acta Neuropathologica Communications
DOI 10.1186/s40478-021-01297-1PMC PMC8684664
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Abstract

Mild traumatic brain injuries (mTBIs) are a prevalent form of injury that can result in persistent neurological impairments. Microglial activation has become increasingly recognized as a key process regulating the pathology of white matter in a wide range of brain injury and disease contexts. As white matter damage is known to be a major contributor to the impairments that follow mTBI, microglia have rightfully become a common target of investigation for the development of mTBI therapies and biomarkers. Recent work has demonstrated that the efficacy of microglial manipulation as a therapeutic intervention following injury or disease is highly time-sensitive, emphasizing the importance of advancing our understanding of the dynamics of post-mTBI microglial activation from onset to resolution. Current reporting of microglial activation in experimental studies of mTBI is non-standardized, which has limited our ability to identify concrete patterns of post-mTBI microglial activation over time. In this review, we examine preclinical studies of mTBI that report on microglial activation in white matter regions to summarize our current understanding of these patterns. Specifically, we summarize timecourses of post-mTBI microglial activation in white matter regions of the brain, identify factors that influence this activation, examine the temporal relationship between microglial activation and other post-mTBI assessments, and compare the relative sensitivities of various methods for detecting microglial activation. While the lack of replicated experimental conditions has limited the extent of conclusions that can confidently be drawn, we find that microglia are activated over a wide range of timecourses following mTBI and that microglial activation is a long-lasting outcome of mTBI that may resolve after most typical post-mTBI assessments, with the exception of those measuring oligodendrocyte lineage cell integrity. We identify several understudied parameters of post-mTBI microglial activation in white matter, such as the inclusion of female subjects. This review summarizes our current understanding of the progression of microglial activation in white matter structures following experimental mTBI and offers suggestions for important future research directions.

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Authors
Velayudhan, P. S., Schwab, N., Hazrati, L.-N., & Wheeler, A. L.
Affiliations
University of Toronto (CA)
Corresponding author
Wheeler, Anne L.
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2021-12-19
Volume
9
Issue
1
Pages
197-197
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-021-01297-1
PMC
PMC8684664
OpenAlex
W4200430228
Cited by
27
References
17
Citations by year
2026: 1 · 2025: 5 · 2024: 3 · 2023: 1 · 2022: 17
FWCI
0.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship@McGill (McGill) (submittedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by)
Funders
Scottish Rite Charitable Foundation of Canada
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
mild traumatic brain injury, microglial activation, white matter, temporal dynamics, oligodendrocyte lineage, sex differences, biomarkers, neuroinflammation
MeSH terms
Animals, Brain Concussion, Time Factors, Microglia, White Matter

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