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Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)

Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. Howeve...

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Autores principales: Krieg, Justin L., Leonard, Anna V., Tuner, Renee J., Corrigan, Frances
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659026/
https://www.ncbi.nlm.nih.gov/pubmed/38028274
http://dx.doi.org/10.1089/neur.2023.0047
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author Krieg, Justin L.
Leonard, Anna V.
Tuner, Renee J.
Corrigan, Frances
author_facet Krieg, Justin L.
Leonard, Anna V.
Tuner, Renee J.
Corrigan, Frances
author_sort Krieg, Justin L.
collection PubMed
description Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI.
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spelling pubmed-106590262023-11-09 Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) Krieg, Justin L. Leonard, Anna V. Tuner, Renee J. Corrigan, Frances Neurotrauma Rep Original Article Traumatic brain injury (TBI) results from mechanical force to the brain and leads to a series of biochemical responses that further damage neurons and supporting cells. Clinically, most TBIs result from an impact to the intact skull, making closed head TBI pre-clinical models highly relevant. However, most of these closed head TBI models use lissencephalic rodents, which may not transduce biomechanical load in the same manner as gyrencephalic humans. To address this translational gap, this study aimed to characterize acute axonal injury and microglial responses in ferrets—the smallest gyrencephalic mammal. Injury was induced in male ferrets (Mustela furo; 1.20–1.51 kg; 6–9 months old) with the novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) model. Animals were randomly allocated to either sham (n = 4), a 22J (joules) impact (n = 4), or a 27J impact (n = 4). Axonal injury was examined histologically with amyloid precursor protein (APP), neurofilament M (RMO 14.9) (RMO-14), and phosphorylated tau (AT180) and the microglial response with ionized calcium-binding adaptor molecule 1 at 24 h post-injury in gray and white matter regions. Graded axonal injury was observed with modest increases in APP and RMO-14 immunoreactivity in the 22J TBI group, mostly within the corpus callosum and fornix and more extensive diffuse axonal injury encompassing gray matter structures like the thalamus and hypothalamus in the 27J group. Accompanying microglial activation was only observed in the 27J group, most prominently within the white matter tracts in response to the larger amounts of axonal injury. The 27J, but not the 22J, group showed an increase in AT180 within the base of the sulci post-injury. This could suggest that the strain may be highest in this region, demonstrating the different responses in gyrencephalic compared to lissencephalic brains. The CHIMERA model in ferrets mimic many of the histopathological features of human closed head TBI acutely and provides a promising model to investigate the pathophysiology of TBI. Mary Ann Liebert, Inc., publishers 2023-11-09 /pmc/articles/PMC10659026/ /pubmed/38028274 http://dx.doi.org/10.1089/neur.2023.0047 Text en © Justin L. Krieg et al., 2023; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Krieg, Justin L.
Leonard, Anna V.
Tuner, Renee J.
Corrigan, Frances
Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title_full Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title_fullStr Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title_full_unstemmed Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title_short Characterization of Traumatic Brain Injury in a Gyrencephalic Ferret Model Using the Novel Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA)
title_sort characterization of traumatic brain injury in a gyrencephalic ferret model using the novel closed head injury model of engineered rotational acceleration (chimera)
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659026/
https://www.ncbi.nlm.nih.gov/pubmed/38028274
http://dx.doi.org/10.1089/neur.2023.0047
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