Mouzon, B., Bachmeier, C., Ojo, J. O., Acker, C., Ferguson, S., Crynen, G., Davies, P., Mullan, M., Stewart, W. and Crawford, F. (2019) Chronic white matter degeneration, but no tau pathology at 1-year post-repetitive mild traumatic brain injury in tau transgenic model. Journal of Neurotrauma, 36(4), pp. 576-588. (doi: 10.1089/neu.2018.5720) (PMID:29993324)
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Abstract
Tau pathology associated with chronic traumatic encephalopathy has been documented in the brains of individuals with a history of repetitive mild traumatic brain injury (r-mTBI). At this stage, the pathobiological role of tau in r-mTBI has not been extensively explored in appropriate preclinical models. Herein, we describe the acute and chronic behavioral and histopathological effects of single and repetitive mild TBI (five injuries given at 48 h intervals) in young adult (3 months old) hTau mice that express all six isoforms of human tau on a null murine background. Animals exposed to r-mTBI showed impaired visuospatial learning in the Barnes maze test that progressively worsened from 2 weeks to 12 months post-injury, which was also accompanied by significant deficits in visuospatial memory consolidation at 12 months post-injury. In contrast, only marginal changes were observed in visuospatial learning at 6 and 12 months following single mTBI. Histopathological analyses revealed that hTau mice developed axonal injury, thinning of the corpus callosum, microgliosis and astrogliosis in the white matter at acute and chronic timepoints following injury. However, tau immunohistochemistry and ELISA data suggest only transient, injury-dependent increases in phosphorylated tau in the cerebral cortex beneath the impact site and in the CA1/CA3 sub-region of the hippocampus after single or r-mTBI. This study implicates white matter degeneration as a prominent feature of survival from mTBI, while the role of tau pathology in the neuropathological sequelae of TBI remains elusive.
Item Type: | Articles |
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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 R01NS038104 & R01NS094, DOD and an NHS Research Scotland Career Researched Fellowship. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Stewart, Dr William |
Authors: | Mouzon, B., Bachmeier, C., Ojo, J. O., Acker, C., Ferguson, S., Crynen, G., Davies, P., Mullan, M., Stewart, W., and Crawford, F. |
College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
Journal Name: | Journal of Neurotrauma |
Publisher: | Mary Ann Liebert |
ISSN: | 0897-7151 |
ISSN (Online): | 1557-9042 |
Published Online: | 11 July 2018 |
Copyright Holders: | Copyright © 2018 Mary Ann Liebert, Inc. |
First Published: | First published in Journal of Neurotrauma 36(4):576-588 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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