Citation

Petraglia AL, Plog BA, Dayawansa S, Chen M, Dashnaw ML, Czerniecka K, Walker CT, Viterise T, Hyrien O, Iliff JJ, Deane R, Nedergaard M, Huang JH. J. Neurotrauma 2014; 31(13): 1211-1224.

Affiliation

University of Rochester Medical Center, Neurosurgery, 601 Elmwood Avenue, Box 670, Rochester, New York, United States, 14586 ; anthony_petraglia@urmc.rochester.edu.

Copyright

(Copyright © 2014, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2013.3255

PMID

24766454

Abstract

There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to un-anesthetized mice. Two-hundred and eighty, 12-week old mice were divided into control, single mild-TBI, and repetitive mild-TBI groups. Repetitive mild-TBI mice received six concussive impacts daily, for seven days. Behavior was assessed at various time-points. Neurological severity score (NSS) was computed and vestibulo-motor function tested with the wire grip test (WGT). Cognitive function was assessed with Morris water maze (MWM); anxiety/risk-taking behavior with the elevated-plus-maze (EPM), and depression-like behavior with the forced swim/tail suspension tests. Sleep EEG/EMG studies were performed at one month. NSS was elevated compared to controls in both TBI groups and improved over time. Repetitive mild-TBI mice demonstrated transient vestibulo-motor deficits on WGT. Repetitive mild-TBI mice also demonstrated deficits in MWM testing. Both mild-TBI groups demonstrated increased anxiety at 2-weeks but repetitive mild-TBI mice develop increased risk-taking behaviors at 1-month that persist at 6-months. Repetitive mild-TBI mice exhibit depression-like behavior at 1-month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mild-TBI in a novel mouse model, which resemble several of the neuro-psychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.

Language: en