Telomere length and advanced diffusion MRI as biomarkers for repetitive mild traumatic brain injury in adolescent rats
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Mild traumatic brain injuries (mTBI) are of worldwide concern in adolescents of both sexes, and repeated mTBI (RmTBI) may have serious long-term neurological consequences. As such, the study of RmTBI and discovery of objective biomarkers that can help guide medical decisions is an important undertaking. Diffusion-weighted MRI (DWI), which provides markers of axonal injury, and telomere length (TL) are two clinically relevant biomarkers that have been implicated in a number of neurological conditions, and may also be affected by RmTBI. Therefore, this study utilized the lateral impact injury model of RmTBI to investigate changes in diffusion MRI and TL, and how these changes relate to each other. Adolescent male and female rats received either three mTBIs or three sham injuries. The first injury was given on postnatal day 30 (P30), with the repeated injuries separated by four days each. Seven days after the final injury, a sample of ear tissue was collected for TL analysis. Rats were then euthanized and whole brains were collected and fixated for MRI analyses that included diffusion and high-resolution structural sequences. Compared to the sham-injured group, RmTBI rats had significantly shorter TL at seven days post-injury. Analysis of advanced DWI measures found that RmTBI rats had abnormalities in the corpus callosum and cortex at seven days post-injury. Notably, many of the DWI changes were correlated with TL. These findings demonstrate that TL and DWI measurements are changed by RmTBI and may represent clinically applicable biomarkers for this.
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Evidence of reductions in telomere length and deficiencies in DNA repair following TBI could predispose neural cells to senescence.
“There is evidence of reductions in telomere length and deficiencies in DNA repair following TBI which could predispose neural cells to senescence [124–126].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [124]
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Sullivan, J., Mirbahai, L., & Lord, J. M. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.10.001 · Cited by 28 · see citing works
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Self-citationDiffusion MRI abnormalities in adolescent rats given repeated mild traumatic brain injury
Wortman, R. C., Meconi, A., Neale, K. J., Brady, R. D., McDonald, S. J., Christie, B. R., Wright, D. K., & Shultz, S. R. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.667 · Cited by 26 · see citing works
Self-citationZamani, A., Ryan, N. P., Wright, D. K., Caeyenberghs, K., & Semple, B. D. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6895 · Cited by 25 · see citing works
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Self-citationThe Neurological Consequences of Engaging in Australian Collision Sports
Symons, G. F., Clough, M., Fielding, J., O’Brien, W. T., Shepherd, C. E., Wright, D. K., & Shultz, S. R. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6884 · Cited by 20 · see citing works
Self-citationSymons, G. F., Clough, M., O’Brien, W. T., Ernest, J., Salberg, S., Costello, D. M., Sun, M., Brady, R. D., McDonald, S. J., Wright, D. K., et al. (2020) · Journal of Concussion · doi:10.1177/2059700220975609 · Cited by 19 · see citing works
Self-citationMcAllister, B. B., Wright, D. K., Wortman, R. C., Shultz, S. R., & Dyck, R. H. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.10.003 · Cited by 19 · see citing works
Self-citationMcCorkle, T. A., Romm, Z. L., & Raghupathi, R. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.04.014 · Cited by 17 · see citing works
Bhatt, D., Hazari, A., Yamakawa, G. R., Salberg, S., Sgro, M., Shultz, S. R., & Mychasiuk, R. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa042 · Cited by 15 · see citing works
Self-citationDill, L. K., Teymornejad, S., Sharma, R., Bozkurt, S., Christensen, J., Chu, E., Rewell, S. S. J., Shad, A., Mychasiuk, R., & Semple, B. D. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114407 · Cited by 14 · see citing works
Self-citationAnimal Models of Traumatic Brain Injury and Their Relevance in Clinical Settings
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Self-citationThe Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases
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Telomerase mRNA-Lipid nanoparticles attenuate neuroinflammation after traumatic brain injury in mice
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Self-citationThe Impact of Concussion, Sport, and Time in Season on Saliva Telomere Length in Healthy Athletes
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Self-citationTelomere Length Associates With Symptom Severity After Mild Traumatic Brain Injury in Older Adults
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Identification of GdRFC1 as a novel regulator of telomerase in Giardia duodenalis
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Self-citationRepeated head impacts establish a senescent cranial bone marrow niche that impairs brain metabolism
Devlin, P. J., Khan, R., Do, T. H., West, B. E., Korf, J. M., Guzman, G. U., Ahn, J., Saltzman, A. B., Jain, A., Tan, C., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03846-8
- Authors
- Wright, D. K., O'Brien, T. J., Mychasiuk, R., & Shultz, S. R.
- Affiliations
- The University of Melbourne (AU)
- The Royal Melbourne Hospital (AU)
- University of Calgary (CA)
- Corresponding author
- Shultz, Sandy R.
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2018
- Volume
- 18
- Pages
- 315-324
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC5987845
- OpenAlex
- W2788141036
- Cited by
- 46
- References
- 81
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 13 · 2019: 5 · 2018: 4
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Health and Medical Research Council (1087172)
- Alberta Children's Hospital Foundation
- 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
- repetitive mild traumatic brain injury, telomere length, diffusion-weighted imaging, biomarkers, axonal injury, adolescent rats, corpus callosum, cortex, sex differences
- MeSH terms
- Analysis of Variance, Animals, Brain Concussion, Brain Mapping, Disease Models, Animal, Female, Image Processing, Computer-Assisted, Male, Neurologic Examination, Sex Factors, Telomere, Rats, Sprague-Dawley, Diffusion Magnetic Resonance Imaging, Rats, Telomere Shortening
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