Inflammation and white matter degeneration persist for years after a single traumatic brain injury

Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H. and Stewart, W. (2013) Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain, 136, pp. 28-42. (doi:10.1093/brain/aws322) (PMCID:PMC3562078)

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Abstract

A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer’s disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer’s disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.

Item Type:Articles
Additional Information:National Institutes of Health grants NS038104 (to D.H.S. and W.S.), AG038911 (to D.H.S.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Dr William and Stewart, Mrs Janice and Begbie, Dr Finn
Authors: Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H., and Stewart, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Brain
Publisher:Oxford University Press
ISSN:0006-8950
ISSN (Online):1460-2156
First Published:First published in Brain: 136: 28-42, 29 January 2013.

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