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Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury

AIM: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. METHODS: EHD2‐sc‐mTNF(R2), an agonist specific for TNFR2, was used to treat neurons expos...

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Autores principales: Gerald, Marcus J., Bracchi‐Ricard, Valerie, Ricard, Jerome, Fischer, Roman, Nandakumar, Bharadwaj, Blumenthal, Gary H., Williams, Raushaun, Kontermann, Roland E., Pfizenmaier, Klaus, Moxon, Karen A., Bethea, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630008/
https://www.ncbi.nlm.nih.gov/pubmed/30941924
http://dx.doi.org/10.1111/cns.13125
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author Gerald, Marcus J.
Bracchi‐Ricard, Valerie
Ricard, Jerome
Fischer, Roman
Nandakumar, Bharadwaj
Blumenthal, Gary H.
Williams, Raushaun
Kontermann, Roland E.
Pfizenmaier, Klaus
Moxon, Karen A.
Bethea, John R.
author_facet Gerald, Marcus J.
Bracchi‐Ricard, Valerie
Ricard, Jerome
Fischer, Roman
Nandakumar, Bharadwaj
Blumenthal, Gary H.
Williams, Raushaun
Kontermann, Roland E.
Pfizenmaier, Klaus
Moxon, Karen A.
Bethea, John R.
author_sort Gerald, Marcus J.
collection PubMed
description AIM: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. METHODS: EHD2‐sc‐mTNF(R2), an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation. RESULTS: The activation of TNFR2 protected neurons from glutamate‐mediated excitotoxicity through the activation of phosphoinositide‐3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2‐sc‐mTNF(R2), but higher levels of neurofilament H and 2′, 3′‐cyclic‐nucleotide 3′‐phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation. CONCLUSION: The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.
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spelling pubmed-66300082019-08-07 Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury Gerald, Marcus J. Bracchi‐Ricard, Valerie Ricard, Jerome Fischer, Roman Nandakumar, Bharadwaj Blumenthal, Gary H. Williams, Raushaun Kontermann, Roland E. Pfizenmaier, Klaus Moxon, Karen A. Bethea, John R. CNS Neurosci Ther Original Articles AIM: The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury. METHODS: EHD2‐sc‐mTNF(R2), an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation. RESULTS: The activation of TNFR2 protected neurons from glutamate‐mediated excitotoxicity through the activation of phosphoinositide‐3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2‐sc‐mTNF(R2), but higher levels of neurofilament H and 2′, 3′‐cyclic‐nucleotide 3′‐phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation. CONCLUSION: The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation. John Wiley and Sons Inc. 2019-04-02 /pmc/articles/PMC6630008/ /pubmed/30941924 http://dx.doi.org/10.1111/cns.13125 Text en © 2019 CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Gerald, Marcus J.
Bracchi‐Ricard, Valerie
Ricard, Jerome
Fischer, Roman
Nandakumar, Bharadwaj
Blumenthal, Gary H.
Williams, Raushaun
Kontermann, Roland E.
Pfizenmaier, Klaus
Moxon, Karen A.
Bethea, John R.
Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title_full Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title_fullStr Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title_full_unstemmed Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title_short Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
title_sort continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630008/
https://www.ncbi.nlm.nih.gov/pubmed/30941924
http://dx.doi.org/10.1111/cns.13125
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