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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6630008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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