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A closed-body preclinical model to investigate blast-induced spinal cord injury

Blast-induced spinal cord injuries (bSCI) are common and account for 75% of all combat-related spinal trauma. It remains unclear how the rapid change in pressure contributes to pathological outcomes resulting from these complex injuries. Further research is necessary to aid in specialized treatments...

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Autores principales: Norris, Carly, Weatherbee, Justin, Murphy, Susan, Marquetti, Izabele, Maniakhina, Lana, Boruch, Alan, VandeVord, Pamela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293620/
https://www.ncbi.nlm.nih.gov/pubmed/37383427
http://dx.doi.org/10.3389/fnmol.2023.1199732
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author Norris, Carly
Weatherbee, Justin
Murphy, Susan
Marquetti, Izabele
Maniakhina, Lana
Boruch, Alan
VandeVord, Pamela
author_facet Norris, Carly
Weatherbee, Justin
Murphy, Susan
Marquetti, Izabele
Maniakhina, Lana
Boruch, Alan
VandeVord, Pamela
author_sort Norris, Carly
collection PubMed
description Blast-induced spinal cord injuries (bSCI) are common and account for 75% of all combat-related spinal trauma. It remains unclear how the rapid change in pressure contributes to pathological outcomes resulting from these complex injuries. Further research is necessary to aid in specialized treatments for those affected. The purpose of this study was to develop a preclinical injury model to investigate the behavior and pathophysiology of blast exposure to the spine, which will bring further insight into outcomes and treatment decisions for complex spinal cord injuries (SCI). An Advanced Blast Simulator was used to study how blast exposure affects the spinal cord in a non-invasive manner. A custom fixture was designed to support the animal in a position that protects the vital organs while exposing the thoracolumbar region of the spine to the blast wave. The Tarlov Scale and Open Field Test (OFT) were used to detect changes in locomotion or anxiety, respectively, 72 h following bSCI. Spinal cords were then harvested and histological staining was performed to investigate markers of traumatic axonal injury (β-APP, NF-L) and neuroinflammation (GFAP, Iba1, S100β). Analysis of the blast dynamics demonstrated that this closed-body model for bSCI was found to be highly repeatable, administering consistent pressure pulses following a Friedlander waveform. There were no significant changes in acute behavior; however, expression of β-APP, Iba1, and GFAP significantly increased in the spinal cord following blast exposure (p < 0.05). Additional measures of cell count and area of positive signal provided evidence of increased inflammation and gliosis in the spinal cord at 72 h after blast injury. These findings indicated that pathophysiological responses from the blast alone are detectable, likely contributing to the combined effects. This novel injury model also demonstrated applications as a closed-body SCI model for neuroinflammation enhancing relevance of the preclinical model. Further investigation is necessary to assess the longitudinal pathological outcomes, combined effects from complex injuries, and minimally invasive treatment approaches.
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spelling pubmed-102936202023-06-28 A closed-body preclinical model to investigate blast-induced spinal cord injury Norris, Carly Weatherbee, Justin Murphy, Susan Marquetti, Izabele Maniakhina, Lana Boruch, Alan VandeVord, Pamela Front Mol Neurosci Molecular Neuroscience Blast-induced spinal cord injuries (bSCI) are common and account for 75% of all combat-related spinal trauma. It remains unclear how the rapid change in pressure contributes to pathological outcomes resulting from these complex injuries. Further research is necessary to aid in specialized treatments for those affected. The purpose of this study was to develop a preclinical injury model to investigate the behavior and pathophysiology of blast exposure to the spine, which will bring further insight into outcomes and treatment decisions for complex spinal cord injuries (SCI). An Advanced Blast Simulator was used to study how blast exposure affects the spinal cord in a non-invasive manner. A custom fixture was designed to support the animal in a position that protects the vital organs while exposing the thoracolumbar region of the spine to the blast wave. The Tarlov Scale and Open Field Test (OFT) were used to detect changes in locomotion or anxiety, respectively, 72 h following bSCI. Spinal cords were then harvested and histological staining was performed to investigate markers of traumatic axonal injury (β-APP, NF-L) and neuroinflammation (GFAP, Iba1, S100β). Analysis of the blast dynamics demonstrated that this closed-body model for bSCI was found to be highly repeatable, administering consistent pressure pulses following a Friedlander waveform. There were no significant changes in acute behavior; however, expression of β-APP, Iba1, and GFAP significantly increased in the spinal cord following blast exposure (p < 0.05). Additional measures of cell count and area of positive signal provided evidence of increased inflammation and gliosis in the spinal cord at 72 h after blast injury. These findings indicated that pathophysiological responses from the blast alone are detectable, likely contributing to the combined effects. This novel injury model also demonstrated applications as a closed-body SCI model for neuroinflammation enhancing relevance of the preclinical model. Further investigation is necessary to assess the longitudinal pathological outcomes, combined effects from complex injuries, and minimally invasive treatment approaches. Frontiers Media S.A. 2023-06-13 /pmc/articles/PMC10293620/ /pubmed/37383427 http://dx.doi.org/10.3389/fnmol.2023.1199732 Text en Copyright © 2023 Norris, Weatherbee, Murphy, Marquetti, Maniakhina, Boruch and VandeVord. 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 Molecular Neuroscience
Norris, Carly
Weatherbee, Justin
Murphy, Susan
Marquetti, Izabele
Maniakhina, Lana
Boruch, Alan
VandeVord, Pamela
A closed-body preclinical model to investigate blast-induced spinal cord injury
title A closed-body preclinical model to investigate blast-induced spinal cord injury
title_full A closed-body preclinical model to investigate blast-induced spinal cord injury
title_fullStr A closed-body preclinical model to investigate blast-induced spinal cord injury
title_full_unstemmed A closed-body preclinical model to investigate blast-induced spinal cord injury
title_short A closed-body preclinical model to investigate blast-induced spinal cord injury
title_sort closed-body preclinical model to investigate blast-induced spinal cord injury
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293620/
https://www.ncbi.nlm.nih.gov/pubmed/37383427
http://dx.doi.org/10.3389/fnmol.2023.1199732
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