学术急诊医学档案

卷 14 编号 1 (2026)

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

学术急诊医学档案, 卷 14 编号 1 (2026), 1 十月 2025 , 第 e46 页
https://doi.org/10.22037/aaem.v14i1.2983

摘要

Introduction: Minocycline as a tetracycline derivative agent with anti-inflammatory and neuroprotective properties, has been investigated in both experimental and clinical settings. This study aimed to evaluated the therapeutic efficacy of Minocycline in acute traumatic spinal cord injury (SCI).

Methods: This systematic review and meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (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 management. 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.

Results: A total of 9 studies met inclusion criteria for qualitative synthesis. 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% confidence interval (CI): 0.95–3.06) for neurological improvement, which did not reach statistical significance.

Conclusion: Current 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.

关键词:
  • Traumatic spinal cord injury
  • minocycline
  • neuroprotection
  • functional recovery
  • histological outcomes
  • motor function

参考

1. Lu Y, Shang Z, Zhang W, Pang M, Hu X, Dai Y, et al. Global incidence and characteristics of spinal cord injury since 2000–2021: a systematic review and meta-analysis. BMC medicine. 2024;22(1):285.

2. Ahuja CS, Wilson JR, Nori S, Kotter M, Druschel C, Curt A, et al. Traumatic spinal cord injury. Nature reviews Disease primers. 2017;3(1):1–21.

3. Aarsland MA, Weber C, Enoksen CH, Dalen I, Tjosevik KE, Oord P, et al. Characteristics and demography of low energy fall injuries in patients> 60 years of age: a population-based analysis over a decade with focus on undertriage. European journal of trauma and emergency surgery. 2024;50(3):995–1001.

4. Malekzadeh H, Golpayegani M, Ghodsi Z, Sadeghi-Naini M, Asgardoon M, Baigi V, et al. Direct cost of illness for spinal cord injury: a systematic review. Global spine journal. 2022;12(6):1267–81.

5. National Spinal Cord Injury Statistical Center. Facts and Figures at a Glance. Birmingham, AL: University of Alabama at Birmingham; 2016.

6. Fehlings MG, Hachem LD, Tetreault LA, Skelly AC, Dettori JR, Brodt ED, et al. Timing of decompressive surgery in patients with acute spinal cord injury: systematic review update. Global spine journal. 2024;14(3_suppl):38S–57S.

7. Fehlings MG, Tetreault LA, Hachem L, Evaniew N, Ganau M, McKenna SL, et al. An update of a clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the role and timing of decompressive surgery. Global Spine Journal. 2024;14(3_suppl):174S–86S.

8. Fehlings MG, Vaccaro A, Wilson JR, Singh A, W. Cadotte D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PloS one. 2012;7(2):e32037.

9. Badhiwala JH, Wilson JR, Witiw CD, Harrop JS, Vaccaro AR, Aarabi B, et al. The influence of timing of surgical decompression for acute spinal cord injury: a pooled analysis of individual patient data. The Lancet Neurology. 2021;20(2):117–26.

10. Fischer G, Bättig L, Stienen MN, Curt A, Fehlings MG, Hejrati N. Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury. Frontiers in Neuroscience. 2024;18:1372920.

11. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. Journal of neurosurgery. 1991;75(1):15–26.

12. Liu Z, Yang Y, He L, Pang M, Luo C, Liu B, et al. High-dose methylprednisolone for acute traumatic spinal cord injury: a meta-analysis. Neurology. 2019;93(9):e841–e50.

13. Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, et al. Efficacy of methylprednisolone in acute spinal cord injury. Jama. 1984;251(1):45–52.

14. Fehlings MG, Wilson JR, Tetreault LA, Aarabi B, Anderson P, Arnold PM, et al. A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the use of methylprednisolone sodium succinate. Global spine journal. 2017;7(3_suppl):203S–11S.

15. Shultz RB, Zhong Y. Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury. Neural Regen Res. 2017;12(5):702–13.

16. Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol. 2004;3(12):744–51.

17. Wang Z, Nong J, Shultz RB, Zhang Z, Kim T, Tom VJ, et al. Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury. Biomaterials. 2017;112:62–71.

18. Papa S, Caron I, Erba E, Panini N, De Paola M, Mariani A, et al. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury. Biomaterials. 2016;75:13–24.

19. Bellver-Landete V, Bretheau F, Mailhot B, Vallières N, Lessard M, Janelle ME, et al. Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury. Nat Commun. 2019;10(1):518.

20. David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 2011;12(7):388–99.

21. Lin F, Liu Y, Luo W, Liu S, Wang Y, Gu R, et al. Minocycline-Loaded poly (α-lipoic acid)–methylprednisolone prodrug nanoparticles for the combined anti-inflammatory treatment of spinal cord injury. International Journal of Nanomedicine. 2022;17:91–104.

22. Bin S, Zhou N, Pan J, Pan F, Wu X-F, Zhou Z-H. Nano-carrier mediated co-delivery of methyl prednisolone and minocycline for improved post-traumatic spinal cord injury conditions in rats. Drug development and industrial pharmacy. 2017;43(6):1033–41.

23. Lee JH, Tigchelaar S, Liu J, Stammers AM, Streijger F, Tetzlaff W, et al. Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Experimental neurology. 2010;225(1):219–30.

24. Ahmad M, Zakaria A, Almutairi KM. Effectiveness of minocycline and FK506 alone and in combination on enhanced behavioral and biochemical recovery from spinal cord injury in rats. Pharmacology Biochemistry and Behavior. 2016;145:45–54.

25. Sencar L, Yilmaz DM, Tuli A, Polat S. Effects of combined treatment of minocycline and methylprednisolone on the expression of tumor necrosis factor alpha and interleukine-6 in experimental spinal cord injury: a light and electron microscopic study. Ultrastructural Pathology. 2020;44(3):283–99.

26. Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John Hurlbert R. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012;135(4):1224–36.

27. Kuhle J, Gaiottino J, Leppert D, Petzold A, Bestwick JP, Malaspina A, et al. Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome. Journal of Neurology, Neurosurgery & Psychiatry. 2015;86(3):273–9.

28. Casha S, Rice T, Stirling DP, Silva C, Gnanapavan S, Giovannoni G, et al. Cerebrospinal fluid biomarkers in human spinal cord injury from a phase II minocycline trial. Journal of neurotrauma. 2018;35(16):1918–28.

29. Meshkini A, Ohadi MAD, Mirghaderi P, Mirzaei F, Rafiei E, Allahyari N, et al. Combined treatment with Minocycline and methylprednisolone in acute traumatic spinal cord injury: A pilot study. Interdisciplinary Neurosurgery. 2024;36:101883.

30. Barker TH, Stone JC, Sears K, Klugar M, Tufanaru C, Leonardi-Bee J, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023;21(3):494–506.

31. Barker TH, Habibi N, Aromataris E, Stone JC, Leonardi-Bee J, Sears K, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for quasi-experimental studies. JBI Evid Synth. 2024;22(3):378–88.

32. An KD, Noh CY, Jang J, Yuh WT, Choi I. Potential Pharmacologic Treatments in Spinal Cord Injury: A Narrative Review. Korean J Neurotrauma. 2025;21(4):237–54.

33. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

  • 摘要 ##plugins.themes.ojsPlusA.frontend.article.viewed##: 10 ##plugins.themes.ojsPlusA.frontend.article.times##
  • pdf (English) ##plugins.themes.ojsPlusA.frontend.article.downloaded##: 20 ##plugins.themes.ojsPlusA.frontend.article.times##

##plugins.themes.ojsPlusA.frontend.article.downloadstatastics##

##plugins.block.makeSubmission.linkLabel##

##plugins.block.makeSubmission.linkLabel##

SJR

SCImago Journal & Country Rank

COPE

最新一期

消息