ReviewSurgical neurology international2026
Neuroprotection or Neurotoxicity? Insights from preclinical and clinical studies of methotrexate in spinal cord injury.
Review in Surgical neurology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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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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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Spinal cord injury (SCI) remains a serious condition with limited treatment options. Methotrexate (MTX), an immunosuppressant with anti-inflammatory and neuroprotective properties, has shown promising effects in experimental SCI, but clinical observations in oncology patients raise concerns regarding neurotoxicity. The aim of this study was to systematically evaluate the effect of MTX on SCI in preclinical models and to compare these findings with available human evidence. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to the end of 2024. Animal studies investigating MTX in SCI were included. Data extraction and quality assessment were performed independently by two reviewers. A random-effects meta-analysis was conducted where appropriate. Human evidence, including large-scale retrospective data, was synthesized for interpretation. Results: Six animal studies (five rats, one rabbit) met the inclusion criteria. MTX administration consistently improved functional recovery, reduced apoptosis, decreased oxidative stress, and improved preservation of myelinated axons. Meta-analysis demonstrated a significant reduction in myeloperoxidase activity (standardized mean differences = -3.40, 95% confidence interval [CI] -5.73 to -1.08, I Conclusion: Preclinical evidence supports MTX as a potential neuroprotective agent in SCI, but human data demonstrate neurotoxicity in noninjured spinal cords, especially with IT use. Differences in route of administration, dosing, host condition, and injury context likely explain this contrast. IT MTX should not be considered in traumatic SCI. Future studies should define safe systemic dosing windows in injured spinal cord models and evaluate cautious early-phase clinical trials under strict monitoring.
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