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Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization

The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending i...

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Autores principales: Corleto, Jose A., Bravo-Hernández, Mariana, Kamizato, Kota, Kakinohana, Osamu, Santucci, Camila, Navarro, Michael R., Platoshyn, Oleksandr, Cizkova, Dasa, Lukacova, Nadezda, Taylor, Julian, Marsala, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705098/
https://www.ncbi.nlm.nih.gov/pubmed/26713446
http://dx.doi.org/10.1371/journal.pone.0144642
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author Corleto, Jose A.
Bravo-Hernández, Mariana
Kamizato, Kota
Kakinohana, Osamu
Santucci, Camila
Navarro, Michael R.
Platoshyn, Oleksandr
Cizkova, Dasa
Lukacova, Nadezda
Taylor, Julian
Marsala, Martin
author_facet Corleto, Jose A.
Bravo-Hernández, Mariana
Kamizato, Kota
Kakinohana, Osamu
Santucci, Camila
Navarro, Michael R.
Platoshyn, Oleksandr
Cizkova, Dasa
Lukacova, Nadezda
Taylor, Julian
Marsala, Martin
author_sort Corleto, Jose A.
collection PubMed
description The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABA(B) receptor agonist), tizanidine (α(2)-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity.
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spelling pubmed-47050982016-01-13 Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization Corleto, Jose A. Bravo-Hernández, Mariana Kamizato, Kota Kakinohana, Osamu Santucci, Camila Navarro, Michael R. Platoshyn, Oleksandr Cizkova, Dasa Lukacova, Nadezda Taylor, Julian Marsala, Martin PLoS One Research Article The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABA(B) receptor agonist), tizanidine (α(2)-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity. Public Library of Science 2015-12-29 /pmc/articles/PMC4705098/ /pubmed/26713446 http://dx.doi.org/10.1371/journal.pone.0144642 Text en © 2015 Corleto et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Corleto, Jose A.
Bravo-Hernández, Mariana
Kamizato, Kota
Kakinohana, Osamu
Santucci, Camila
Navarro, Michael R.
Platoshyn, Oleksandr
Cizkova, Dasa
Lukacova, Nadezda
Taylor, Julian
Marsala, Martin
Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title_full Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title_fullStr Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title_full_unstemmed Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title_short Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization
title_sort thoracic 9 spinal transection-induced model of muscle spasticity in the rat: a systematic electrophysiological and histopathological characterization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705098/
https://www.ncbi.nlm.nih.gov/pubmed/26713446
http://dx.doi.org/10.1371/journal.pone.0144642
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