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Minocycline in Acute Traumatic Spinal Cord Injury: A Systematic Review and Exploratory Meta Analysis of Preclinical and Clinical Evidence

Fahim, F.; Tabasi Kakhki, F.; Qahremani, R.; Faramin Lashkarian, M.; Ghaffari, A.; Moosavian, S. M.; Jafari, M.; Ebrahimabad, M.; Ghasemi, M.; Mahmoodi, H.; Bahmaie Kamaei, S.; Oveisi, S.; Oraee Yazdani, S.; Zali, A.

2025-12-22 neurology
10.64898/2025.12.19.25342695 medRxiv
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BackgroundTraumatic spinal cord injury (SCI) is a major cause of long-term neurological disability, with limited pharmacological therapies targeting secondary inflammatory and neurodegenerative injury mechanisms. Minocycline, a tetracycline derivative with anti-inflammatory and neuroprotective properties, has been investigated in both experimental and clinical settings; however, its therapeutic efficacy in acute traumatic SCI remains uncertain. MethodsA systematic review was conducted in accordance with PRISMA 2020 guidelines. Major electronic databases were comprehensively searched to identify preclinical animal studies and human clinical studies evaluating minocycline, alone or in combination therapies, for acute traumatic SCI. Risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools tailored to study design. Qualitative synthesis included all eligible studies, while quantitative synthesis was restricted to clinical studies reporting extractable effect estimates for neurological improvement. ResultsA total of 11 studies met inclusion criteria for qualitative synthesis, including experimental animal studies and human clinical investigations. Preclinical studies demonstrated consistent biological effects of minocycline on inflammatory markers, oxidative stress, and histopathological outcomes, particularly in combination therapies, although functional recovery with minocycline monotherapy was inconsistent. Clinical studies indicated that minocycline was generally well tolerated; however, most trials did not demonstrate statistically significant improvements in neurological or functional outcomes. Only two clinical studies provided suitable data for meta-analysis, yielding a pooled odds ratio of 1.70 (95% CI 0.95-3.06) for neurological improvement, which did not reach statistical significance. ConclusionCurrent evidence suggests that while minocycline exhibits promising biological activity and an acceptable safety profile in acute traumatic SCI, robust clinical efficacy has not been conclusively demonstrated. Well-designed, adequately powered randomized controlled trials with standardized outcome reporting are required to determine whether these biological effects translate into meaningful functional recovery.

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