Sex matters: repetitive mild traumatic brain injury in adolescent rats
Open accessAbstract
Objective: Whether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (Rm TBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI. Methods: Rats were given a single mTBI, RmTBI (i.e., 3 x), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety‐ and depressive‐like behavior. Postmortem analyses investigated gene expression and structural changes in the brain. Results: Many of the outcomes exhibited a sex‐dependent response to RmTBI. While all rats given RmTBI had deficits in balance, motor coordination, locomotion, and anxiety‐like behavior, only male rats given RmTBI had short‐term working memory deficits, whereas only females given RmTBI had increased depressive‐like behavior. Volumetric and diffusion weighted MRI analyses found that while RmTBI‐induced atrophy of the prefrontal cortex was greater in female rats, only the male rats exhibited worse white matter integrity in the corpus callosum following RmTBI. Sex‐dependent changes in brain expression of mRNA for glial fibrillary acidic protein, myelin basic protein, and tau protein were also observed following injury. Interpretation: These findings suggest that in adolescent mTBI, sex matters; and future studies incorporating both male and females are warranted to provide a greater understanding of injury prognosis and better inform clinical practice.
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Gene expression in males and females varied based on the direction of acceleration and rotational forces and number of head impacts.
“Gene expression in males and females also varied based on the direction of acceleration and rotational forces and number of head impacts. 44,45”
From Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know (2019) · cites this paper as [45]
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Sex Differences in Traumatic Brain Injury: What We Know and What We Should Know
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- Authors
- Wright, D. K., O'Brien, T. J., Shultz, S. R., & Mychasiuk, R.
- Affiliations
- The University of Melbourne (AU)
- The Royal Melbourne Hospital (AU)
- University of Calgary (CA)
- Corresponding author
- Mychasiuk, Richelle
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2017-07-26
- Volume
- 4
- Issue
- 9
- Pages
- 640-654
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC5590540
- OpenAlex
- W2737058806
- Cited by
- 119
- References
- 74
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 14 · 2020: 21 · 2019: 23 · 2018: 10 · 2017: 3
- FWCI
- 12.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Funders
- Alberta Children's Hospital Foundation
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, repetitive mild traumatic brain injury, sex differences, adolescent rats, working memory deficits, depression-like behavior, anxiety-like behavior, motor coordination deficits, glial fibrillary acidic protein, myelin basic protein, tau protein, gene expression
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