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Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model

Repetitive mild traumatic brain injuries (rmTBI) may contribute to the development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects and via regulation of neuronal synaptic plasticity by counteracting pos...

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Autores principales: Hiskens, Matthew I., Li, Katy M., Schneiders, Anthony G., Fenning, Andrew S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514484/
https://www.ncbi.nlm.nih.gov/pubmed/37745053
http://dx.doi.org/10.3389/fphar.2023.1254382
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author Hiskens, Matthew I.
Li, Katy M.
Schneiders, Anthony G.
Fenning, Andrew S.
author_facet Hiskens, Matthew I.
Li, Katy M.
Schneiders, Anthony G.
Fenning, Andrew S.
author_sort Hiskens, Matthew I.
collection PubMed
description Repetitive mild traumatic brain injuries (rmTBI) may contribute to the development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects and via regulation of neuronal synaptic plasticity by counteracting post-trauma excitotoxicity. This study aimed to investigate mechanisms implicated in the etiology of neurodegeneration in rmTBI mice treated with ALC. Adult male C57BL/6J mice were allocated to sham, rmTBI or ALC + rmTBI groups. 15 rmTBIs were administered across 23 days using a modified weight drop model. Neurological testing and spatial learning and memory assessments via the Morris Water Maze (MWM) were undertaken at 48 h and 3 months. RT-PCR analysis of the cortex and hippocampus was undertaken for MAPT, GFAP, AIF1, GRIA, CCL11, TDP43, and TNF genes. Gene expression in the cortex showed elevated mRNA levels of MAPT, TNF, and GFAP in the rmTBI group that were reduced by ALC treatment. In the hippocampus, mRNA expression was elevated for GRIA1 in the rmTBI group but not the ALC + rmTBI treatment group. ALC treatment showed protective effects against the deficits displayed in neurological testing and MWM assessment observed in the rmTBI group. While brain structures display differential vulnerability to insult as evidenced by location specific postimpact disruption of key genes, this study shows correlative mRNA neurodegeneration and functional impairment that was ameliorated by ALC treatment in several key genes. ALC may mitigate damage inflicted in the various secondary neurodegenerative cascades and contribute to functional protection following rmTBI.
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spelling pubmed-105144842023-09-23 Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model Hiskens, Matthew I. Li, Katy M. Schneiders, Anthony G. Fenning, Andrew S. Front Pharmacol Pharmacology Repetitive mild traumatic brain injuries (rmTBI) may contribute to the development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects and via regulation of neuronal synaptic plasticity by counteracting post-trauma excitotoxicity. This study aimed to investigate mechanisms implicated in the etiology of neurodegeneration in rmTBI mice treated with ALC. Adult male C57BL/6J mice were allocated to sham, rmTBI or ALC + rmTBI groups. 15 rmTBIs were administered across 23 days using a modified weight drop model. Neurological testing and spatial learning and memory assessments via the Morris Water Maze (MWM) were undertaken at 48 h and 3 months. RT-PCR analysis of the cortex and hippocampus was undertaken for MAPT, GFAP, AIF1, GRIA, CCL11, TDP43, and TNF genes. Gene expression in the cortex showed elevated mRNA levels of MAPT, TNF, and GFAP in the rmTBI group that were reduced by ALC treatment. In the hippocampus, mRNA expression was elevated for GRIA1 in the rmTBI group but not the ALC + rmTBI treatment group. ALC treatment showed protective effects against the deficits displayed in neurological testing and MWM assessment observed in the rmTBI group. While brain structures display differential vulnerability to insult as evidenced by location specific postimpact disruption of key genes, this study shows correlative mRNA neurodegeneration and functional impairment that was ameliorated by ALC treatment in several key genes. ALC may mitigate damage inflicted in the various secondary neurodegenerative cascades and contribute to functional protection following rmTBI. Frontiers Media S.A. 2023-09-08 /pmc/articles/PMC10514484/ /pubmed/37745053 http://dx.doi.org/10.3389/fphar.2023.1254382 Text en Copyright © 2023 Hiskens, Li, Schneiders and Fenning. https://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 Pharmacology
Hiskens, Matthew I.
Li, Katy M.
Schneiders, Anthony G.
Fenning, Andrew S.
Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title_full Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title_fullStr Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title_full_unstemmed Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title_short Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model
title_sort repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-l-carnitine in a preclinical model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514484/
https://www.ncbi.nlm.nih.gov/pubmed/37745053
http://dx.doi.org/10.3389/fphar.2023.1254382
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