title: The use of telomere length as a predictive biomarker for injury prognosis in juvenile rats following a concussion/mild traumatic brain injury.
abstract: Telomeres were originally believed to be passive players in cellular replication, but recent research has highlighted their more active role in epigenetic patterning and promotion of cellular growth and survival. Furthermore, literature demonstrates that telomere length (TL) is responsive to environmental manipulations such as prenatal stress and dietary programming. As the search for a prognostic biomarker of concussion has had limited success, this study sought to examine whether or not telomere length (TL) could be an efficacious predictor of symptom severity in juvenile rats following concussion. Rats from four distinct experimental groups (caloric restriction (CR), high fat diet (HFD), exercise (EX), and standard controls (STD)) received a mild traumatic brain injury (mTBI)/concussion and were then subjected to a behavioural test battery. The test battery was scored and the animals were categorized as poor, average, or good, based on their performance on the 6 tests examined. Skin cells (from ear notch samples) were taken 17days post-injury and DNA was extracted for telomere length analysis. Ear notch skin cell TL was highly correlated with brain tissue TL for a given individual. Animals in the CR and EX cohorts had significantly longer telomeres, while animals in the HFD cohort had significantly shorter telomeres, when compared to controls. The mTBI/concussion reduced TL in all cohorts except the EX group. A significant linear relationship was found between TL and performance on the behavioural test battery, whereby shorter telomeres were associated with poorer performance and longer telomeres with better performance. As performance on the test battery is linked to symptom severity, this study found TL to be a reasonable tool for concussion prognosis. Future studies with human populations should examine the validity of TL in peripheral cells, as a predictor of concussion pathology.
authors.affiliation: Alberta Children's Hospital Research Foundation, University of Calgary, Faculty of Medicine, Calgary, AB, Canada.
authors.forename: Harleen
authors.initials: H
authors.lastname: Hehar
authors.affiliation: Alberta Children's Hospital Research Foundation, University of Calgary, Faculty of Medicine, Calgary, AB, Canada. Electronic address: rmmychas@ucalgary.ca.
authors.forename: Richelle
authors.initials: R
authors.lastname: Mychasiuk
mesh_terms: D000818:Animals; D001924:Brain Concussion / Q000175:diagnosis* / Q000503:physiopathology*; D015331:Cohort Studies; D059305:Diet, High-Fat; D004038:Diet, Reducing; D004195:Disease Models, Animal; D004423:Ear; D005260:Female; D016014:Linear Models; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology*; D011379:Prognosis; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening / Q000502:physiology
keywords: Caloric restriction; Exercise; High fat diet; Programming; Recovery