Examining Mgat5 upregulation's protective effects and underlying mechanisms in spinal cord injury

Secondary inflammation severely hinders recovery after spinal cord injury (SCI). This study investigates whether boosting Mgat5-mediated N-glycosylation via a lentiviral vector can reprogram the local immune microenvironment and foster functional repair.

We engineered a lentiviral vector to overexpress Mgat5 (Lv-Mgat5) and validated it in rat dorsal root ganglion cells. Next, we established a contusion SCI model in rats, dividing them into sham, SCI, MP (methylprednisolone), Lv-vector, and Lv-Mgat5 groups. Motor recovery was evaluated using BBB and inclined plane tests. To uncover the mechanisms, we quantified N-glycan branching (PHA-L precipitation), inflammatory cytokines (ELISA), and regeneration markers (Western blot).

Lv-Mgat5 effectively upregulated β-1,6-GlcNAc branching both in vitro and in vivo without cytotoxicity. Importantly, this targeted intervention modulated the injured spinal cord microenvironment toward an anti-inflammatory profile. We observed a significant drop in TNF-α and IL-1β, alongside a surge in IL-10 (p < 0.05). Furthermore, GAP-43 expression remained robustly elevated. Consequently, rats treated with Lv-Mgat5 showed remarkable and sustained improvements in hindlimb motor function compared to vehicle controls (p < 0.01).

Targeted Mgat5 upregulation effectively modulates the post-injury microenvironment. By reshaping the N-glycosylation profile, it attenuates secondary neuroinflammation and supports a regeneration-associated molecular response, offering a promising target for gene therapy after SCI.