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Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain

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 casualtie...

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Autores principales: Arun, Peethambaran, Rossetti, Franco, Wilder, Donna M., Sajja, Sujith, Van Albert, Stephen A., Wang, Ying, Gist, Irene D., Long, Joseph B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253679/
https://www.ncbi.nlm.nih.gov/pubmed/32508743
http://dx.doi.org/10.3389/fneur.2020.00438
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author Arun, Peethambaran
Rossetti, Franco
Wilder, Donna M.
Sajja, Sujith
Van Albert, Stephen A.
Wang, Ying
Gist, Irene D.
Long, Joseph B.
author_facet Arun, Peethambaran
Rossetti, Franco
Wilder, Donna M.
Sajja, Sujith
Van Albert, Stephen A.
Wang, Ying
Gist, Irene D.
Long, Joseph B.
author_sort Arun, Peethambaran
collection PubMed
description 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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spelling pubmed-72536792020-06-05 Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain Arun, Peethambaran Rossetti, Franco Wilder, Donna M. Sajja, Sujith Van Albert, Stephen A. Wang, Ying Gist, Irene D. Long, Joseph B. Front Neurol Neurology 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. Frontiers Media S.A. 2020-05-21 /pmc/articles/PMC7253679/ /pubmed/32508743 http://dx.doi.org/10.3389/fneur.2020.00438 Text en Copyright © 2020 Arun, Rossetti, Wilder, Sajja, Van Albert, Wang, Gist and Long. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Arun, Peethambaran
Rossetti, Franco
Wilder, Donna M.
Sajja, Sujith
Van Albert, Stephen A.
Wang, Ying
Gist, Irene D.
Long, Joseph B.
Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title_full Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title_fullStr Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title_full_unstemmed Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title_short Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain
title_sort blast exposure leads to accelerated cellular senescence in the rat brain
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253679/
https://www.ncbi.nlm.nih.gov/pubmed/32508743
http://dx.doi.org/10.3389/fneur.2020.00438
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