ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Attenuating Neurogenic Sympathetic Hyperreflexia Robustly Improves Antibacterial Immunity After Chronic Spinal Cord Injury.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury-associated immunodepression syndrome.Neural regeneration research · 2026Article
- Article
- NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury.Communications biology · 2025Article
- Evolving insights on the role of microglia in neuroinflammation, plasticity, and regeneration of the injured spinal cord.Frontiers in immunology · 2025Review
- Valsalva maneuver pressure recovery time is prolonged following spinal cord injury with correlations to autonomically-influenced secondary complications.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024Article
- Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury.bioRxiv : the preprint server for biology · 2024Article
- Mechanistic involvement of noradrenergic neuronal neurotransmitter release in cutaneous vasoconstriction during autonomic dysreflexia in persons with spinal cord injury.Autonomic neuroscience : basic & clinical · 2024Article
- Consequences of spinal cord injury on the sympathetic nervous system.Frontiers in cellular neuroscience · 2023Review
- Proinflammatory and Immunomodulatory Gene and Protein Expression Patterns in Spinal Cord and Spleen Following Acute and Chronic High Thoracic Injury.Journal of inflammation research · 2023Article
- Elevated levels of IgA and IgG2 in individuals with chronic spinal cord injury.The journal of spinal cord medicine · 2022Observational
- Maladaptation of renal hemodynamics contributes to kidney dysfunction resulting from thoracic spinal cord injury in mice.American journal of physiology. Renal physiology · 2022Article
- Spinal Cord Injury Impairs Lung Immunity in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Immune dysfunction after spinal cord injury - A review of autonomic and neuroendocrine mechanisms.Current opinion in pharmacology · 2022Review
- Thoracic VGluT2The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Review
- Toward rebalancing blood pressure instability after spinal cord injury with spinal cord electrical stimulation: A mini review and critique of the evolving literature.Autonomic neuroscience : basic & clinical · 2022Review
- Resveratrol Can Attenuate Astrocyte Activation to Treat Spinal Cord Injury by Inhibiting Inflammatory Responses.Molecular neurobiology · 2021Review
- Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury.Biology · 2021Review
- Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord.Journal of neuroinflammation · 2020Article
- Grafting Embryonic Raphe Neurons Reestablishes Serotonergic Regulation of Sympathetic Activity to Improve Cardiovascular Function after Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Spinal cord injury (SCI) disrupts critical physiological systems, including the cardiovascular and immune system. Plasticity of spinal circuits below the injury results in abnormal, heightened sympathetic responses, such as extreme, sudden hypertension that hallmarks life-threatening autonomic dysreflexia. Moreover, such sympathetic hyperreflexia detrimentally impacts other effector organs, including the spleen, resulting in spinal cord injury-induced immunodeficiency. Consequently, infection is a leading cause of mortality after SCI. Unfortunately, there are no current treatments that prophylactically limit sympathetic hyperreflexia to prevent subsequent effector organ dysfunction. The cytokine soluble tumor necrosis factor α (sTNFα) is upregulated in the CNS within minutes after SCI and remains elevated. Here, we report that commencing intrathecal administration of XPro1595, an inhibitor of sTNFα, at a clinically feasible, postinjury time point (i.e., 3 d after complete SCI) sufficiently diminishes maladaptive plasticity within the spinal sympathetic reflex circuit. This results in less severe autonomic dysreflexia, a real-time gauge of sympathetic hyperreflexia, for months postinjury. Remarkably, delayed delivery of the sTNFα inhibitor prevents sympathetic hyperreflexia-associated splenic atrophy and loss of leukocytes to dramatically improve the endogenous ability of chronic SCI rats to fight off pneumonia, a common cause of hospitalization after injury. The improved immune function with XPro1595 correlates with less noradrenergic fiber sprouting and normalized norepinephrine levels in the spleen, indicating that heightened, central sTNFα signaling drives peripheral, norepinephrine-mediated organ dysfunction, a novel mechanism of action. Thus, our preclinical study supports intrathecally targeting sTNFα as a viable strategy to broadly attenuate sympathetic dysregulation, thereby improving cardiovascular regulation and immunity long after SCI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.