Efficacy of Minocycline in Acute Traumatic Spinal Cord Injury

Traumatic spinal cord injury (SCI) leads to irreversible neurological deficits, and no acute pharmacologic therapy has demonstrated consistent benefit. Minocycline, a tetracycline antibiotic with anti-inflammatory and neuroprotective properties, has been proposed as a therapeutic candidate. We performed a PRISMA-guided systematic review of PubMed and Embase (January 2000-July 2024) to evaluate minocycline in acute SCI. Twenty-six studies met the inclusion criteria, comprising three human trials and 23 animal studies. In humans, intravenous minocycline (200-400 mg daily for 7 days) achieved cerebrospinal fluid concentrations of ∼2.3 µg/mL, below the therapeutic range suggested by preclinical models (35-75 µg/mL). Cervical SCI patients showed numerically greater motor recovery (+14 American Spinal Cord Injury Association motor points vs. controls), but findings were underpowered and did not consistently reach significance. Biomarker modulation, including reduced HO-1 and NfL levels, suggested biological activity yet failed to translate into functional improvement. Animal studies demonstrated consistent benefits, with higher Basso, Beattie, and Bresnahan locomotor scores (14.6 ± 0.6 vs. 8.3 ± 0.7 at 28 days, p < 0.001), reduced lesion volume by up to 58%, preserved white matter, and attenuation of inflammatory, apoptotic, and oxidative cascades in a dose- and route-dependent manner. Overall, minocycline exerts robust neuroprotective effects in preclinical SCI but limited functional benefit in humans, largely due to subtherapeutic central nervous system penetration at tolerated systemic doses. Future trials should explore optimized delivery strategies, include demographic stratification, and employ standardized functional endpoints to better define translational potential.