A 72-h sedated porcine model of traumatic spinal cord injury

Mathias Møller Thygesen; Seyar Entezari; Nanna Houlind; Teresa Haugaard Nielsen; Nicholas Østergaard Olsen; Tim Damgaard Nielsen; Mathias Skov; Joel Borgstedt-Bendixen; Alp Tankisi; Mads Rasmussen; Halldór Bjarki Einarsson; Peter Agger; Dariusz Orlowski; Stig Eric Dyrskog; Line Thorup; Michael Pedersen; Mikkel Mylius Rasmussen

doi:10.1016/j.bas.2024.102813

A 72-h sedated porcine model of traumatic spinal cord injury

Mathias Møller Thygesen^*, Seyar Entezari, Nanna Houlind, Teresa Haugaard Nielsen, Nicholas Østergaard Olsen, Tim Damgaard Nielsen, Mathias Skov, Joel Borgstedt-Bendixen, Alp Tankisi, Mads Rasmussen, Halldór Bjarki Einarsson, Peter Agger, Dariusz Orlowski, Stig Eric Dyrskog, Line Thorup, Michael Pedersen, Mikkel Mylius Rasmussen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

Original language	English
Article number	102813
Journal	Brain and Spine
Volume	4
Number of pages	9
ISSN	2772-5294
DOIs	https://doi.org/10.1016/j.bas.2024.102813
Publication status	Published - Apr 2024

Keywords

Critical care model
Diffusion magnetic resonance imaging
Translational animal model
Traumatic spinal cord injury

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Thygesen, M. M., Entezari, S., Houlind, N., Nielsen, T. H., Olsen, N. Ø., Nielsen, T. D., Skov, M., Borgstedt-Bendixen, J., Tankisi, A., Rasmussen, M., Einarsson, H. B., Agger, P., Orlowski, D., Dyrskog, S. E., Thorup, L., Pedersen, M., & Rasmussen, M. M. (2024). A 72-h sedated porcine model of traumatic spinal cord injury. Brain and Spine, 4, Article 102813. https://doi.org/10.1016/j.bas.2024.102813

@article{08ecaa8ea7fa406490e680c65342a462,

title = "A 72-h sedated porcine model of traumatic spinal cord injury",

abstract = "Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.",

keywords = "Critical care model, Diffusion magnetic resonance imaging, Translational animal model, Traumatic spinal cord injury",

author = "Thygesen, {Mathias M{\o}ller} and Seyar Entezari and Nanna Houlind and Nielsen, {Teresa Haugaard} and Olsen, {Nicholas {\O}stergaard} and Nielsen, {Tim Damgaard} and Mathias Skov and Joel Borgstedt-Bendixen and Alp Tankisi and Mads Rasmussen and Einarsson, {Halld{\'o}r Bjarki} and Peter Agger and Dariusz Orlowski and Dyrskog, {Stig Eric} and Line Thorup and Michael Pedersen and Rasmussen, {Mikkel Mylius}",

note = "{\textcopyright} 2024 The Authors.",

year = "2024",

month = apr,

doi = "10.1016/j.bas.2024.102813",

language = "English",

volume = "4",

journal = "Brain and Spine",

issn = "2772-5294",

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TY - JOUR

T1 - A 72-h sedated porcine model of traumatic spinal cord injury

AU - Thygesen, Mathias Møller

AU - Entezari, Seyar

AU - Houlind, Nanna

AU - Nielsen, Teresa Haugaard

AU - Olsen, Nicholas Østergaard

AU - Nielsen, Tim Damgaard

AU - Skov, Mathias

AU - Borgstedt-Bendixen, Joel

AU - Tankisi, Alp

AU - Rasmussen, Mads

AU - Einarsson, Halldór Bjarki

AU - Agger, Peter

AU - Orlowski, Dariusz

AU - Dyrskog, Stig Eric

AU - Thorup, Line

AU - Pedersen, Michael

AU - Rasmussen, Mikkel Mylius

PY - 2024/4

Y1 - 2024/4

N2 - Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

AB - Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

KW - Critical care model

KW - Diffusion magnetic resonance imaging

KW - Translational animal model

KW - Traumatic spinal cord injury

UR - http://www.scopus.com/inward/record.url?scp=85190499439&partnerID=8YFLogxK

U2 - 10.1016/j.bas.2024.102813

DO - 10.1016/j.bas.2024.102813

M3 - Journal article

C2 - 38681174

SN - 2772-5294

VL - 4

JO - Brain and Spine

JF - Brain and Spine

M1 - 102813

ER -

A 72-h sedated porcine model of traumatic spinal cord injury

Abstract

Keywords

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