Comparative Neuroprotective Effects of Minocycline and Bone Marrow Mononuclear Cells After Complete Spinal Cord Transection in Adult Rats
Acute spinal cord injury triggers a complex secondary injury cascade characterized by lesion expansion, neuroinflammation, glial reactivity, and oligodendrocyte degeneration, which together limit endogenous repair. Identifying neuroprotective interventions capable of targeting distinct components of this cascade remains a major challenge. In this study, we compared the neuroprotective profiles of minocycline, a tetracycline derivative with anti-inflammatory and antioxidant properties, and bone marrow mononuclear cells (BMMCs), which exert paracrine immunomodulatory and trophic effects, using a model of complete thoracic spinal cord transection in adult rats. Animals received either BMMCs (5 x 106 cells, intravenously, 24 h post-injury) or minocycline (50 mg/kg twice daily for 48 h, followed by 25 mg/kg for five days). Histological and immunohistochemical analyses revealed that both treatments attenuated secondary damage, reducing lesion area, microglial/macrophage activation (ED1+ cells), and oligodendrocyte pathology (Tau-1+ cells). However, the magnitude and pattern of protection differed between interventions: minocycline produced a stronger reduction in lesion area, whereas BMMCs exerted greater suppression of microglial/macrophage activation and superior preservation of oligodendrocytes. Astrocyte counts (GFAP+ cells) did not differ quantitatively among groups, despite qualitative differences in astrocytic morphology. Integrated effect size analysis further highlighted these complementary neuroprotective profiles across outcomes. Collectively, these findings indicate that minocycline and BMMCs target distinct components of secondary injury after severe spinal cord injury, providing a mechanistic rationale for future studies exploring multi-targeted or combinatorial therapeutic strategies.