Journal article
Mitigating sTNF/TNFR1 activation on VGluT2 + spinal cord interneurons improves immune function after mid-thoracic spinal cord injury
Brain, behavior, and immunity, v 123, pp 633-643
Jan 2025
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual’s outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kβ dependent in VGluT2 + INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.
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Details
- Title
- Mitigating sTNF/TNFR1 activation on VGluT2 + spinal cord interneurons improves immune function after mid-thoracic spinal cord injury
- Creators
- Tetyana Martynyuk - Drexel UniversityJerome Ricard - Drexel UniversityValerie Bracchi-Ricard - Drexel UniversitySamuel Price - Drexel UniversityJenna R. McGrath - Drexel UniversityKimberly J. Dougherty - Drexel UniversityVeronica Tom - Drexel UniversityJohn R. Bethea - Drexel University
- Publication Details
- Brain, behavior, and immunity, v 123, pp 633-643
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- National Institutes of Health: R01 NS111761, T32 NS121768
This work is supported by National Institutes of Health grants R01 NS111761 (J.R.B.) Collaboration with Dr. Kimberly J. Dougherty and Jenna R. McGrath is supported by T32 NS121768 (J.R.M) . We thank Mr. Jeffrey Faust for expert technical and experimental guidance with flow cytometry and Dr. Harini Sreenivasappa for expert assistance in confocal imaging at Drexel's Cell Imaging Center.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Neurobiology and Anatomy; Registered Nurse (RN) to Bachelor of Science in Nursing (BSN); College of Arts and Sciences; College of Medicine
- Web of Science ID
- WOS:001340408800001
- Scopus ID
- 2-s2.0-85206460367
- Other Identifier
- 991021929345004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Neurosciences
- Psychiatry