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Journal article
Pharmacological Inhibition of Soluble Tumor Necrosis Factor-Alpha Two Weeks after High Thoracic Spinal Cord Injury Does Not Affect Sympathetic Hyperreflexia
Journal of neurotrauma, v 38(15), pp 2186-2191
01 Aug 2021
PMID: 33397170
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning ∼2 weeks post-injury (wpi). The neuroimmune system has been implicated in driving sympathetic hyperreflexia, as inhibition of the cytokine soluble tumor necrosis factor-alpha (sTNFα) using the biological mimetic XPro1595 beginning within days post-SCI has been shown to attenuate the development of AD. Here, we sought to further understand the effective therapeutic time window of XPro1595 to diminish sympathetic hyperreflexia, as indicated by AD. We delayed the commencement of continuous intrathecal administration of XPro1595 until 2 weeks after a complete, thoracic level 3 injury in adult rats. We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNFα inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNFα signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.
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Details
- Title
- Pharmacological Inhibition of Soluble Tumor Necrosis Factor-Alpha Two Weeks after High Thoracic Spinal Cord Injury Does Not Affect Sympathetic Hyperreflexia
- Creators
- Micaela L O'Reilly - Department of Neurobiology and Anatomy, Marion Murray Spinal Cord Research Center, Drexel University College of Medicine, Philadelphia, Pennsylvania, USAEugene Mironets - Drexel UniversityTatiana M Shapiro - Drexel UniversityKallon Crowther - Drexel UniversityEileen Collyer - Drexel UniversityJohn R Bethea - Drexel UniversityVeronica J Tom - Drexel University
- Publication Details
- Journal of neurotrauma, v 38(15), pp 2186-2191
- Publisher
- Mary Ann Liebert
- Grant note
- R01 NS111761 / NINDS NIH HHS R01 NS085426 / NINDS NIH HHS R01 NS106908 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000614554000001
- Scopus ID
- 2-s2.0-85108172324
- Other Identifier
- 991019168954904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences