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Journal article
Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
CNS neuroscience & therapeutics, v 25(8), pp 884-893
01 Aug 2019
PMID: 30941924
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury
- Creators
- Marcus J. Gerald - Drexel UniversityValerie Bracchi-Ricard - Drexel UniversityJerome Ricard - Drexel UniversityRoman Fischer - Drexel UniversityBharadwaj Nandakumar - Drexel UniversityGary H. Blumenthal - Drexel UniversityRaushaun Williams - Drexel UniversityRoland E. Kontermann - University of StuttgartKlaus Pfizenmaier - University of StuttgartKaren A. Moxon - Drexel UniversityJohn R. Bethea - Drexel University
- Publication Details
- CNS neuroscience & therapeutics, v 25(8), pp 884-893
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- R01NS051709-14 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01NS051709 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) FI 2138/1-1 / Deutsche Forschungsgemeinschaft; German Research Foundation (DFG)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000475623000009
- Scopus ID
- 2-s2.0-85063789377
- Other Identifier
- 991019167658604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy