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Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points

The cumulative effect of mild traumatic brain injuries (mTBI) can result in chronic neurological damage, however the molecular mechanisms underpinning this detriment require further investigation. A closed head weight drop model that replicates the biomechanics and head acceleration forces of human...

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Autores principales: Hiskens, Matthew I., Schneiders, Anthony G., Vella, Rebecca K., Fenning, Andrew S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104440/
https://www.ncbi.nlm.nih.gov/pubmed/33961674
http://dx.doi.org/10.1371/journal.pone.0251315
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author Hiskens, Matthew I.
Schneiders, Anthony G.
Vella, Rebecca K.
Fenning, Andrew S.
author_facet Hiskens, Matthew I.
Schneiders, Anthony G.
Vella, Rebecca K.
Fenning, Andrew S.
author_sort Hiskens, Matthew I.
collection PubMed
description The cumulative effect of mild traumatic brain injuries (mTBI) can result in chronic neurological damage, however the molecular mechanisms underpinning this detriment require further investigation. A closed head weight drop model that replicates the biomechanics and head acceleration forces of human mTBI was used to provide an exploration of the acute and chronic outcomes following single and repeated impacts. Adult male C57BL/6J mice were randomly assigned into one of four impact groups (control; one, five and 15 impacts) which were delivered over 23 days. Outcomes were assessed 48 hours and 3 months following the final mTBI. Hippocampal spatial learning and memory assessment revealed impaired performance in the 15-impact group compared with control in the acute phase that persisted at chronic measurement. mRNA analyses were performed on brain tissue samples of the cortex and hippocampus using quantitative RT-PCR. Eight genes were assessed, namely MAPT, GFAP, AIF1, GRIA1, CCL11, TARDBP, TNF, and NEFL, with expression changes observed based on location and follow-up duration. The cortex and hippocampus showed vulnerability to insult, displaying upregulation of key excitotoxicity and inflammation genes. Serum samples showed no difference between groups for proteins phosphorylated tau and GFAP. These data suggest that the cumulative effect of the impacts was sufficient to induce mTBI pathophysiology and clinical features. The genes investigated in this study provide opportunity for further investigation of mTBI-related neuropathology and may provide targets in the development of therapies that help mitigate the effects of mTBI.
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spelling pubmed-81044402021-05-18 Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points Hiskens, Matthew I. Schneiders, Anthony G. Vella, Rebecca K. Fenning, Andrew S. PLoS One Research Article The cumulative effect of mild traumatic brain injuries (mTBI) can result in chronic neurological damage, however the molecular mechanisms underpinning this detriment require further investigation. A closed head weight drop model that replicates the biomechanics and head acceleration forces of human mTBI was used to provide an exploration of the acute and chronic outcomes following single and repeated impacts. Adult male C57BL/6J mice were randomly assigned into one of four impact groups (control; one, five and 15 impacts) which were delivered over 23 days. Outcomes were assessed 48 hours and 3 months following the final mTBI. Hippocampal spatial learning and memory assessment revealed impaired performance in the 15-impact group compared with control in the acute phase that persisted at chronic measurement. mRNA analyses were performed on brain tissue samples of the cortex and hippocampus using quantitative RT-PCR. Eight genes were assessed, namely MAPT, GFAP, AIF1, GRIA1, CCL11, TARDBP, TNF, and NEFL, with expression changes observed based on location and follow-up duration. The cortex and hippocampus showed vulnerability to insult, displaying upregulation of key excitotoxicity and inflammation genes. Serum samples showed no difference between groups for proteins phosphorylated tau and GFAP. These data suggest that the cumulative effect of the impacts was sufficient to induce mTBI pathophysiology and clinical features. The genes investigated in this study provide opportunity for further investigation of mTBI-related neuropathology and may provide targets in the development of therapies that help mitigate the effects of mTBI. Public Library of Science 2021-05-07 /pmc/articles/PMC8104440/ /pubmed/33961674 http://dx.doi.org/10.1371/journal.pone.0251315 Text en © 2021 Hiskens et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hiskens, Matthew I.
Schneiders, Anthony G.
Vella, Rebecca K.
Fenning, Andrew S.
Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title_full Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title_fullStr Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title_full_unstemmed Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title_short Repetitive mild traumatic brain injury affects inflammation and excitotoxic mRNA expression at acute and chronic time-points
title_sort repetitive mild traumatic brain injury affects inflammation and excitotoxic mrna expression at acute and chronic time-points
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104440/
https://www.ncbi.nlm.nih.gov/pubmed/33961674
http://dx.doi.org/10.1371/journal.pone.0251315
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