ArticleJournal of neuroinflammation2014
Central but not systemic administration of XPro1595 is therapeutic following moderate spinal cord injury in mice.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- The Role of Tumor Necrosis Factor Following Spinal Cord Injury: A Systematic Review.Cellular and molecular neurobiology · 2023Pooled it
- Etanercept in Spinal Cord Injury: A Systematic Review.Brain sciences · 2026Review
- The heme-binding protein hemopexin promotes functional recovery and tissue protection after spinal cord injury via sex-specific regulation of inflammation and ferroptosis.Journal of neuroinflammation · 2025Article
- Systemic inhibition of soluble TNF significantly changes glial cell populations leading to improved myelin integrity and better functional outcome after experimental stroke.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Microglial TNFR2 signaling regulates the inflammatory response after CNS injury in a sex-specific fashion.Brain, behavior, and immunity · 2024Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Article
- Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review.Frontiers in immunology · 2023Review
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- Article
- Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression.Frontiers in cardiovascular medicine · 2022Article
- Fundamentally different roles of neuronal TNF receptors in CNS pathology: TNFR1 and IKKβ promote microglial responses and tissue injury in demyelination while TNFR2 protects against excitotoxicity in mice.Journal of neuroinflammation · 2021Article
- Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury.Biology · 2021Review
- Hydrogel-based local drug delivery strategies for spinal cord repair.Neural regeneration research · 2021Review
- TNFα in MS and Its Animal Models: Implications for Chronic Pain in the Disease.Frontiers in neurology · 2021Review
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- Neuroimmune System as a Driving Force for Plasticity Following CNS Injury.Frontiers in cellular neuroscience · 2020Review
- Selective Targeting of TNF Receptors as a Novel Therapeutic Approach.Frontiers in cell and developmental biology · 2020Review
- Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development.Oxidative medicine and cellular longevity · 2020Review
- Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury.British journal of anaesthesia · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundGlial cell activation and overproduction of inflammatory mediators in the central nervous system (CNS) have been implicated in acute traumatic injuries to the CNS, including spinal cord injury (SCI). Elevated levels of the proinflammatory cytokine tumor necrosis factor (TNF), which exists in both a soluble (sol) and a transmembrane (tm) form, have been found in the lesioned cord early after injury. The contribution of solTNF versus tmTNF to the development of the lesion is, however, still unclear.
methodsWe tested the effect of systemically or centrally blocking solTNF alone, using XPro1595, versus using the drug etanercept to block both solTNF and tmTNF compared to a placebo vehicle following moderate SCI in mice. Functional outcomes were evaluated using the Basso Mouse Scale, rung walk test, and thermal hyperalgesia analysis. The inflammatory response in the lesioned cord was investigated using immunohistochemistry and western blotting analyses.
resultsWe found that peripheral administration of anti-TNF therapies had no discernable effect on locomotor performances after SCI. In contrast, central administration of XPro1595 resulted in improved locomotor function, decreased anxiety-related behavior, and reduced damage to the lesioned spinal cord, whereas central administration of etanercept had no therapeutic effects. Improvements in XPro1595-treated mice were accompanied by increases in Toll-like receptor 4 and TNF receptor 2 (TNFR2) protein levels and changes in Iba1 protein expression in microglia/macrophages 7 and 28 days after SCI.
conclusionsThese studies suggest that, by selectively blocking solTNF, XPro1595 is neuroprotective when applied directly to the lesioned cord. This protection may be mediated via alteration of the inflammatory environment without suppression of the neuroprotective effects of tmTNF signaling through TNFR2.
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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.