Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
Open accessAbstract
Blast-induced traumatic brain injury (bTBI) is one of the major causes of persistent disabilities in Service Members, and a history of bTBI has been identified as a primary risk factor for developing age-associated neurodegenerative diseases. Clinical observations of several military blast casualties have revealed a rapid age-related loss of white matter integrity in the brain. In the present study, we have tested the effect of single and tightly coupled repeated blasts on cellular senescence in the rat brain. Isoflurane-anesthetized rats were exposed to either a single or 2 closely coupled blasts in an advanced blast simulator. Rats were euthanized and brains were collected at 24 h, 1 month and 1 year post-blast to determine senescence-associated-β-galactosidase (SA-β-gal) activity in the cells using senescence marker stain. Single and repeated blast exposures resulted in significantly increased senescence marker staining in several neuroanatomical structures, including cortex, auditory cortex, dorsal lateral thalamic nucleus, geniculate nucleus, superior colliculus, ventral thalamic nucleus and hippocampus. In general, the increases in SA-β-gal activity were more pronounced at 1 month than at 24 h or 1 year post-blast and were also greater after repeated than single blast exposures. Real-time quantitative RT-PCR analysis revealed decreased levels of mRNA for senescence marker protein-30 (SMP-30) and increased mRNA levels for p21 (cyclin dependent kinase inhibitor 1A, CDKN1A), two other related protein markers of cellular senescence. The increased senescence observed in some of these affected brain structures may be implicated in several long-term sequelae after exposure to blast, including memory disruptions and impairments in movement, auditory and ocular functions.
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Accumulation of DNA damage has been reported in various models of mTBI.
“accumulation of DNA damage has been reported in various models of mTBI [3, 123, 151]”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [3]
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Tang, S., Xu, S., Wilder, D. M., Medina, A. E., Li, X., Fiskum, G. M., Li, J., Kakulavarapu, V. R., Long, J. B., Gullapalli, R. P., et al. (2024) · Neurotrauma Reports · doi:10.1089/neur.2024.0002 · Cited by 9 · see citing works
Self-citationArun, P., Rossetti, F., Eken, O., Wilder, D. M., Wang, Y., & Long, J. B. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2021.0144 · Cited by 8 · see citing works
Self-citationArun, P., Rossetti, F., Wilder, D. M., Wang, Y., Gist, I. D., & Long, J. B. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.652190 · Cited by 7 · see citing works
Self-citationBraga, M. F. M., Juranek, J. J., Eiden, L. E., Li, Z., Figueiredo, T. H., Furtado, M. D. A., & Marini, A. M. (2022) · Amino Acids · doi:10.1007/s00726-022-03184-y · Cited by 8 · see citing works
Zeng, H., Zhao, S., Pang, Z., Wang, S., Cao, L., & Zhang, Y. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2202044 · Cited by 5 · see citing works
Blast Exposure Alters Synaptic Connectivity in the Mouse Auditory Cortex
Wang, Y., Wei, Y., Ren, M., Sajja, V. S. S. S., Wilder, D. M., Arun, P., Gist, I. D., Long, J. B., & Yang, F. (2024) · Journal of Neurotrauma · doi:10.1089/neu.2023.0348 · Cited by 3 · see citing works
Self-citationExline, J. E., Volyanyuk, M., Lotesto, K. M., Segismundo, A. B., Byram, S. C., & Foecking, E. M. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149611 · Cited by 3 · see citing works
Kozlova, Y. V. (2021) · Neurophysiology · doi:10.1007/s11062-022-09921-z · Cited by 3 · see citing works
Phuyal, G., Govindarajulu, M., Al-Lami, A., Thanapaul, R. J. R. S., Pundkar, C. Y., Sajja, V. S. S. S., Long, J. B., & Arun, P. (2025) · Journal of Neurotrauma · doi:10.1177/08977151251395742 · Cited by 3 · see citing works
Self-citationRitzel, R. M., Li, Y., Lei, Z., Carter, J., He, J., Choi, H., Khan, N., Li, H., Allen, S., Lipinski, M. M., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-1021695/v1 · Cited by 2 · see citing works
Thanapaul, R. J. R. S., Govindarajulu, M., Pundkar, C. Y., & Arun, P. (2026) · Military Medical Research · doi:10.1016/j.mmr.2026.100014 · Cited by 1 · see citing works
Self-citationRusling, M., DeMar, J. C., Chakraborty, N., Hoke, A. V., Miller, S., Rosenberger, J. G., Batuure, A., Wilder, D. M., Sajja, V. S. S. S., Long, J. B., et al. (2024) · Frontiers in Microbiomes · doi:10.3389/frmbi.2024.1430340
Self-citationCellular senescence and senolytic therapy in traumatic brain injury
Brann, D. W., Singh, H. D., Wang, J., Lu, Y., Carr, C., & Dhandapani, K. M. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1862748
- Authors
- Arun, P., Rossetti, F., Wilder, D. M., Sajja, S., Van Albert, S. A., Wang, Y., Gist, I. D., & Long, J. B.
- Affiliations
- Walter Reed Army Institute of Research (US)
- Corresponding author
- Arun, Peethambaran
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2020-05-21
- Volume
- 11
- Pages
- 438-438
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC7253679
- OpenAlex
- W3026083465
- Cited by
- 30
- References
- 70
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 5 · 2021: 9
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Army Materiel Command
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- blast-induced traumatic brain injury, cellular senescence, senescence-associated β-galactosidase, p21, white matter integrity, age-related neurodegeneration, hippocampus, thalamic nuclei, superior colliculus, auditory cortex, geniculate nucleus
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