Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats

We hypothesized that the acute response to traumatic brain injury (TBI) shares mechanisms with brain plasticity in the kindling model. Utilizing two unique, complementary strains of inbred rats, selected to be either susceptible or resistant to seizure-induced plasticity evoked by kindling of the pe...

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Autores principales: Kotloski, Robert J., Rutecki, Paul A., Sutula, Thomas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968787/
https://www.ncbi.nlm.nih.gov/pubmed/31998207
http://dx.doi.org/10.3389/fneur.2019.01286
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author Kotloski, Robert J.
Rutecki, Paul A.
Sutula, Thomas P.
author_facet Kotloski, Robert J.
Rutecki, Paul A.
Sutula, Thomas P.
author_sort Kotloski, Robert J.
collection PubMed
description We hypothesized that the acute response to traumatic brain injury (TBI) shares mechanisms with brain plasticity in the kindling model. Utilizing two unique, complementary strains of inbred rats, selected to be either susceptible or resistant to seizure-induced plasticity evoked by kindling of the perforant path, we examined acute electrophysiological alterations and differences in brain-derived neurotrophic factor (BDNF) protein concentrations after a moderate-to-severe brain injury. At baseline, limited strain-dependent differences in acute electrophysiological activity were found, and no differences in BDNF. Following injury, pronounced strain-dependent differences in electrophysiologic activity were noted at 0.5 min. However, the divergence is transient, with diminished differences at 5 min after injury and no differences at 10 and 15 min after injury. Strain-specific differences in BDNF protein concentration were noted 4 h after injury. A simple risk score model generated by machine learning and based solely on post-injury electrophysiologic activity at the 0.5-min timepoint distinguished perforant path kindling susceptible (PPKS) rats from non-plasticity-susceptible strains. The findings demonstrate that genetic background which affects brain circuit plasticity also affects acute response to TBI. An improved understanding of the effect of genetic background on the cellular, molecular, and circuit plasticity mechanisms activated in response to TBI and their timecourse is key in developing much-needed novel therapeutic approaches.
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spelling pubmed-69687872020-01-29 Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats Kotloski, Robert J. Rutecki, Paul A. Sutula, Thomas P. Front Neurol Neurology We hypothesized that the acute response to traumatic brain injury (TBI) shares mechanisms with brain plasticity in the kindling model. Utilizing two unique, complementary strains of inbred rats, selected to be either susceptible or resistant to seizure-induced plasticity evoked by kindling of the perforant path, we examined acute electrophysiological alterations and differences in brain-derived neurotrophic factor (BDNF) protein concentrations after a moderate-to-severe brain injury. At baseline, limited strain-dependent differences in acute electrophysiological activity were found, and no differences in BDNF. Following injury, pronounced strain-dependent differences in electrophysiologic activity were noted at 0.5 min. However, the divergence is transient, with diminished differences at 5 min after injury and no differences at 10 and 15 min after injury. Strain-specific differences in BDNF protein concentration were noted 4 h after injury. A simple risk score model generated by machine learning and based solely on post-injury electrophysiologic activity at the 0.5-min timepoint distinguished perforant path kindling susceptible (PPKS) rats from non-plasticity-susceptible strains. The findings demonstrate that genetic background which affects brain circuit plasticity also affects acute response to TBI. An improved understanding of the effect of genetic background on the cellular, molecular, and circuit plasticity mechanisms activated in response to TBI and their timecourse is key in developing much-needed novel therapeutic approaches. Frontiers Media S.A. 2020-01-10 /pmc/articles/PMC6968787/ /pubmed/31998207 http://dx.doi.org/10.3389/fneur.2019.01286 Text en Copyright © 2020 Kotloski, Rutecki and Sutula. 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
Kotloski, Robert J.
Rutecki, Paul A.
Sutula, Thomas P.
Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title_full Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title_fullStr Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title_full_unstemmed Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title_short Genetic Background Influences Acute Response to TBI in Kindling-Susceptible, Kindling-Resistant, and Outbred Rats
title_sort genetic background influences acute response to tbi in kindling-susceptible, kindling-resistant, and outbred rats
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968787/
https://www.ncbi.nlm.nih.gov/pubmed/31998207
http://dx.doi.org/10.3389/fneur.2019.01286
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