Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats

Eric Eyolfson; Glenn R Yamakawa; Yannick Griep; Reid Collins; Thomas Carr; Melinda Wang; Alexander W Lohman; Richelle Mychasiuk

doi:10.1093/texcom/tgaa002

Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats

Cereb Cortex Commun. 2020 Feb 20;1(1):tgaa002. doi: 10.1093/texcom/tgaa002. eCollection 2020.

Authors

Eric Eyolfson^{1

2}, Glenn R Yamakawa³, Yannick Griep^{1

2

4

5}, Reid Collins^{1

2}, Thomas Carr^{6

7}, Melinda Wang^{1

2}, Alexander W Lohman^{6

7}, Richelle Mychasiuk^{1

2

3}

Affiliations

¹ Department of Psychology, Alberta Children's Hospital Research Institute, The University of Calgary, Calgary, AB, T2N 1N4, Canada.
² Department of Psychology, Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, T2N 1N4, Canada.
³ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia.
⁴ Division of Epidemiology, Stress Research Institute, Stockholm University, 106 91 Stockholm, Sweden.
⁵ Behavioral Science Institute, Radbound University, 9104, 6500 HE, Nijmegen, The Netherlands.
⁶ Department of Cell Biology and Anatomy, Alberta Children's Hospital Research Institute, The University of Calgary, Calgary, AB, T2N 1N4, Canada.
⁷ Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, The University of Calgary, Calgary, AB, T2N 1N4, Canada.

Abstract

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.

Keywords: GFAP; IBA1; adolescence; concussion; sex differences; telomere length.