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A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury

Spinal cord injury (SCI) is a devastating neurological condition with no effective treatment. Hypothermia induced by physical means (cold fluid) is established as an effective therapy in animal models of SCI, but its clinical translation to humans is hampered by several constraints. Hypothermia indu...

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Autores principales: Sarkar, Amrita, Kim, Kevin T., Tsymbalyuk, Orest, Keledjian, Kaspar, Wilhelmy, Bradley E., Sherani, Nageen A., Jia, Xiaofeng, Gerzanich, Volodymyr, Simard, J. Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231662/
https://www.ncbi.nlm.nih.gov/pubmed/35675523
http://dx.doi.org/10.1089/ther.2021.0013
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author Sarkar, Amrita
Kim, Kevin T.
Tsymbalyuk, Orest
Keledjian, Kaspar
Wilhelmy, Bradley E.
Sherani, Nageen A.
Jia, Xiaofeng
Gerzanich, Volodymyr
Simard, J. Marc
author_facet Sarkar, Amrita
Kim, Kevin T.
Tsymbalyuk, Orest
Keledjian, Kaspar
Wilhelmy, Bradley E.
Sherani, Nageen A.
Jia, Xiaofeng
Gerzanich, Volodymyr
Simard, J. Marc
author_sort Sarkar, Amrita
collection PubMed
description Spinal cord injury (SCI) is a devastating neurological condition with no effective treatment. Hypothermia induced by physical means (cold fluid) is established as an effective therapy in animal models of SCI, but its clinical translation to humans is hampered by several constraints. Hypothermia induced pharmacologically may be noninferior or superior to physically induced hypothermia for rapid, convenient systemic temperature reduction, but it has not been investigated previously in animal models of SCI. We used a rat model of SCI to compare outcomes in three groups: (1) normothermic controls; (2) hypothermia induced by conventional physical means; (3) hypothermia induced by intravenous (IV) dihydrocapsaicin (DHC). Male rats underwent unilateral lower cervical SCI and were treated after a 4-hour delay with physical cooling or IV DHC (∼0.60 mg/kg total) cooling (both 33.0 ± 1.0°C) lasting 4 hours; controls were kept normothermic. Telemetry was used to monitor temperature and heart rate during and after treatments. In two separate experiments, one ending at 48 hours, the other at 6 weeks, “blinded” investigators evaluated rats in the three groups for neurological function followed by histopathological evaluation of spinal cord tissues. DHC reliably induced systemic cooling to 32–33°C. At both the time points examined, the two modes of hypothermia yielded similar improvements in neurological function and lesion size compared with normothermic controls. Our results indicate that DHC-induced hypothermia may be comparable with physical hypothermia in efficacy, but more clinically feasible to administer than physical hypothermia.
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spelling pubmed-92316622022-06-27 A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury Sarkar, Amrita Kim, Kevin T. Tsymbalyuk, Orest Keledjian, Kaspar Wilhelmy, Bradley E. Sherani, Nageen A. Jia, Xiaofeng Gerzanich, Volodymyr Simard, J. Marc Ther Hypothermia Temp Manag Original Articles Spinal cord injury (SCI) is a devastating neurological condition with no effective treatment. Hypothermia induced by physical means (cold fluid) is established as an effective therapy in animal models of SCI, but its clinical translation to humans is hampered by several constraints. Hypothermia induced pharmacologically may be noninferior or superior to physically induced hypothermia for rapid, convenient systemic temperature reduction, but it has not been investigated previously in animal models of SCI. We used a rat model of SCI to compare outcomes in three groups: (1) normothermic controls; (2) hypothermia induced by conventional physical means; (3) hypothermia induced by intravenous (IV) dihydrocapsaicin (DHC). Male rats underwent unilateral lower cervical SCI and were treated after a 4-hour delay with physical cooling or IV DHC (∼0.60 mg/kg total) cooling (both 33.0 ± 1.0°C) lasting 4 hours; controls were kept normothermic. Telemetry was used to monitor temperature and heart rate during and after treatments. In two separate experiments, one ending at 48 hours, the other at 6 weeks, “blinded” investigators evaluated rats in the three groups for neurological function followed by histopathological evaluation of spinal cord tissues. DHC reliably induced systemic cooling to 32–33°C. At both the time points examined, the two modes of hypothermia yielded similar improvements in neurological function and lesion size compared with normothermic controls. Our results indicate that DHC-induced hypothermia may be comparable with physical hypothermia in efficacy, but more clinically feasible to administer than physical hypothermia. Mary Ann Liebert, Inc., publishers 2022-06-01 2022-06-07 /pmc/articles/PMC9231662/ /pubmed/35675523 http://dx.doi.org/10.1089/ther.2021.0013 Text en © Amrita Sarkar et al., 2022; 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 Articles
Sarkar, Amrita
Kim, Kevin T.
Tsymbalyuk, Orest
Keledjian, Kaspar
Wilhelmy, Bradley E.
Sherani, Nageen A.
Jia, Xiaofeng
Gerzanich, Volodymyr
Simard, J. Marc
A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title_full A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title_fullStr A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title_full_unstemmed A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title_short A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury
title_sort direct comparison of physical versus dihydrocapsaicin-induced hypothermia in a rat model of traumatic spinal cord injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231662/
https://www.ncbi.nlm.nih.gov/pubmed/35675523
http://dx.doi.org/10.1089/ther.2021.0013
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