Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury

Pischiutta, F. et al. (2018) Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury. Experimental Neurology, 300, pp. 167-178. (doi: 10.1016/j.expneurol.2017.11.003) (PMID:29126888)

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There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: − 30%) and external capsule (EC: − 21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (− 17%) and EC (− 13%), corresponding to histopathological evidence of white matter loss (cl-CC: − 68%; cl-EC: − 30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Stewart, Dr William and Hay, Dr Jennifer
Authors: Pischiutta, F., Micotti, E., Hay, J. R., Marongiu, I., Sammali, E., Tolomeo, D., Vegliante, G., Stocchetti, N., Forloni, G., De Simoni, M.-G., Stewart, W., and Zanier, E. R.
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:Experimental Neurology
ISSN (Online):1090-2430
Published Online:07 November 2017
Copyright Holders:Copyright © 2017 Elsevier Inc.
First Published:First published in Experimental Neurology 300: 167-178
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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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