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

Autor: Gerald MJ; Department of Biology, Drexel University, Philadelphia, Pennsylvania., Bracchi-Ricard V; Department of Biology, Drexel University, Philadelphia, Pennsylvania., Ricard J; Department of Biology, Drexel University, Philadelphia, Pennsylvania., Fischer R; Department of Biology, Drexel University, Philadelphia, Pennsylvania., Nandakumar B; Department of Biomedical Engineering, Drexel University, Philadelphia, Pennsylvania.; Department of Biomedical Engineering, University of California-Davis, Davis, California., Blumenthal GH; Department of Biomedical Engineering, Drexel University, Philadelphia, Pennsylvania.; Department of Biomedical Engineering, University of California-Davis, Davis, California., Williams R; Department of Biology, Drexel University, Philadelphia, Pennsylvania., Kontermann RE; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; Stuttgart Research Center Systems Biology, University of Stuttgart, Stuttgart, Germany., Pfizenmaier K; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; Stuttgart Research Center Systems Biology, University of Stuttgart, Stuttgart, Germany., Moxon KA; Department of Biomedical Engineering, Drexel University, Philadelphia, Pennsylvania.; Department of Biomedical Engineering, University of California-Davis, Davis, California., Bethea JR; Department of Biology, Drexel University, Philadelphia, Pennsylvania.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2019 Aug; Vol. 25 (8), pp. 884-893. Date of Electronic Publication: 2019 Apr 02.
DOI: 10.1111/cns.13125
Abstrakt: 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.
(© 2019 CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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