Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Mouzon, B. C. et al. (2018) Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury. Annals of Clinical and Translational Neurology, 5(1), pp. 64-80. (doi:10.1002/acn3.510) (PMID:29376093) (PMCID:PMC5771321)

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Abstract

Objective: Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival. Methods: Male C57BL/6J mice (aged 2–3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety-like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies. Results: At 24 months survival animals exposed to r-mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule-motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI. Interpretation: In this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.

Item Type:Articles
Additional Information:This research was funded by a Department of Defense award (W81XWH-10-1-0759) to Dr. Fiona Crawford, and by the Roskamp Foundation. Dr. Crawford is a VA Research Career Scientist. Dr. Stewart is supported by NIH grants NS038104 & NS094003, DOD grant PT110785 and an NHS Research Scotland Career Researched Fellowship.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Dr William
Authors: Mouzon, B. C., Bachmeier, C., Ojo, J. O., Acker, C. M., Ferguson, S., Paris, D., Ait-Ghezala, G., Crynen, G., Davies, P., Mullan, M., Stewart, W., and Crawford, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Annals of Clinical and Translational Neurology
Publisher:Wiley
ISSN:2328-9503
ISSN (Online):2328-9503
Published Online:14 December 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Annals of Clinical and Translational Neurology 5(1):64-80
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
696421Characterising amyloid pathologies after traumatic brain injuryWilliam StewartNational Institute of Health (NIH-BETH)2R01NS038104-15A1RI NEUROSCIENCE & PSYCHOLOGY