Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes

Mouzon, B., Chaytow, H., Crynen, G., Bachmeier, C., Stewart, J., Mullan, M., Stewart, W. and Crawford, F. (2013) Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes. Journal of Neurotrauma, 29(18), pp. 2761-2773. (doi:10.1089/neu.2012.2498)

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Abstract

Concussion or mild traumatic brain injury (mTBI) represents the most common type of brain injury. However, in contrast with moderate or severe injury, there are currently few non-invasive experimental studies that investigate the cumulative effects of repetitive mTBI using rodent models. Here we describe and compare the behavioral and pathological consequences in a mouse model of single (s-mTBI) or repetitive injury (r-mTBI, five injuries given at 48 h intervals) administered by an electromagnetic controlled impactor. Our results reveal that a single mTBI is associated with transient motor and cognitive deficits as demonstrated by rotarod and the Barnes Maze respectively, whereas r-mTBI results in more significant deficits in both paradigms. Histology revealed no overt cell loss in the hippocampus, although a reactive gliosis did emerge in hippocampal sector CA1 and in the deeper cortical layers beneath the injury site in repetitively injured animals, where evidence of focal injury also was observed in the brainstem and cerebellum. Axonal injury, manifest as amyloid precursor protein immunoreactive axonal profiles, was present in the corpus callosum of both injury groups, though more evident in the r-mTBI animals. Our data demonstrate that this mouse model of mTBI is reproducible, simple, and noninvasive, with behavioral impairment after a single injury and increasing deficits after multiple injuries accompanied by increased focal and diffuse pathology. As such, this model may serve as a suitable platform with which to explore repetitive mTBI relevant to human brain injury.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Dr William and Stewart, Mrs Janice
Authors: Mouzon, B., Chaytow, H., Crynen, G., Bachmeier, C., Stewart, J., Mullan, M., Stewart, W., and Crawford, F.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Neurotrauma
Publisher:Mary Ann Liebert
ISSN:0897-7151
ISSN (Online):1557-9042
Published Online:23 November 2012

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