Journal article
NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury
Communications biology, v 8(1), 787
22 May 2025
PMID: 40404889
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Heightened sympathetic reflexes (sympathetic hyperreflexia, SH) post-high-level spinal cord injury (SCI) detrimentally impact effector organs, resulting in peripheral immune dysfunction and cardiovascular disease, two leading causes of morbidity and mortality in SCI. We previously found that an activated neuroimmune system after SCI contributes to intraspinal plasticity in the spinal sympathetic reflex (SSR) circuit, underlying SH. We hypothesize that activation of NF-κB, a key regulator of inflammation, in spinal cord below-SCI contributes to driving SSR circuit plasticity, resulting in SH-associated autonomic dysreflexia (AD) and peripheral immune dysfunction. Here, we demonstrate inhibition of central NF-κB signaling via intrathecal delivery of dimethylamino parthenolide (DMAPT) significantly decreases SH post-complete transection of thoracic spinal segment 3 in adult rats. This included reduced AD severity that was associated with decreased interneuron recruitment into the SSR circuit after SCI. We also observed intrathecal DMAPT-treatment improved survival post-SCI that corresponded with normalized numbers of splenic regulatory T-cells. These findings underscore central NF-κB signaling as a key component driving SH after SCI.
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Details
- Title
- NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury
- Creators
- Micaela L O'Reilly - Drexel UniversityMariah J Wulf - Drexel UniversityTheresa M Connors - Drexel UniversityYing Jin - Drexel UniversityFrank Bearoff - Temple UniversityNan Hai - Drexel UniversityJulien Bouyer - Drexel UniversitySandhya Kortagere - Drexel UniversityYinghui Zhong - Drexel UniversityJohn R Bethea - George Washington UniversityVeronica J Tom - Drexel University
- Publication Details
- Communications biology, v 8(1), 787
- Publisher
- Nature Publishing Group
- Number of pages
- 18
- Grant note
- F31NS118841 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) T32NS121768 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS085426 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS106908 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS122371 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS111761 / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Biology; Neurobiology and Anatomy; College of Arts and Sciences; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001493152500002
- Scopus ID
- 2-s2.0-105005785746
- Other Identifier
- 991022054028104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology