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Cited by 1,001Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchNeuroinflammation and Neurodegeneration Mechanisms

Inflammation after trauma: Microglial activation and traumatic brain injury

Ramlackhansingh, Anil F., Brooks, David J., Greenwood, Richard J., Bose, Subrata K., Turkheimer, Federico E., Kinnunen, Kirsi M., Gentleman, Steve, Heckemann, Rolf A. +3 more·2011·Annals of Neurology
DOI 10.1002/ana.22455
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Abstract

Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. ANN NEUROL 2011;

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  • Imaging studies show increased binding of PK-[11C](R)PK11195 ligand, expressed by activated microglia, between 11 months and 17 years post-injury.

    “and imaging studies showing increased binding of PK-[11C](R)PK11195 ligand, expressed by activated microglia, between 11 months and 17 years post-injury (86).”

    From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [86]

  • In human patients, increased microglial activation is detectable by PET scan 17 years after primary injury.

    “In human patients, increased microglial activation is even detectable by PET scan 17 years after the primary injury [114].”

    From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [114]

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Authors
Ramlackhansingh, A. F., Brooks, D. J., Greenwood, R. J., Bose, S. K., Turkheimer, F. E., Kinnunen, K. M., Gentleman, S., Heckemann, R. A., Gunanayagam, K., Gelosa, G., & Sharp, D. J.
Affiliations
  • Hammersmith Hospital (GB)
  • UCL Queen Square Institute of Neurology (GB)
  • Goldsmiths University of London (GB)
Corresponding author
Sharp, David J.
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2011-06-27
Volume
70
Issue
3
Pages
374-383
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.22455
OpenAlex
W2096019298
Cited by
999
References
32
Citations by year
2026: 40 · 2025: 57 · 2024: 60 · 2023: 62 · 2022: 71 · 2021: 104 · 2020: 92 · 2019: 86 · 2018: 66 · 2017: 71 · 2016: 71 · 2015: 75 · 2014: 58 · 2013: 49 · 2012: 31
FWCI
28.64
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Imperial College Healthcare Charity
  • Dunhill Medical Trust
  • Medical Research Council
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
traumatic brain injury, microglial activation, neuroinflammation, [11C]PK11195 PET, thalamus, cognitive impairment, subcortical structures, diffusion tensor imaging, structural brain abnormalities
MeSH terms
Adult, Amnesia, Brain Injuries, Cognition Disorders, Educational Status, Female, Humans, Image Processing, Computer-Assisted, Inflammation, Isoquinolines, Macrophage Activation, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Neuropsychological Tests, Thalamus, Wechsler Scales, Glasgow Coma Scale, Cluster Analysis, Microglia, Positron-Emission Tomography, Diffusion Tensor Imaging, Executive Function

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