Spinal cord transverse section hinders Wallerian degeneration and neoangiogenesis after peripheral nerve transection: Involvement of Schwann cells' miR-134-5p.

Patients with spinal cord injury (SCI) frequently develop chronic wounds in paralyzed limbs, underscoring the importance of neural regulation and peripheral nerve integrity for tissue repair; however, it remains unclear how concomitant SCI alters the distal responses to peripheral nerve injury (PNI) and the associated microRNA (miRNA) profile. Sprague-Dawley rats underwent sciatic nerve transection alone (PNI group) or complete spinal cord transection at L1-L2 combined with sciatic transection (SCI+PNI group), and distal sciatic nerve stumps were harvested at 0, 3, and 7 days for gross observation, H&E and toluidine blue staining, myelin basic protein (MBP) immunofluorescence, transmission electron microscopy, and CD31 immunohistochemistry to assess Wallerian degeneration and angiogenesis; miRNA expression profiles were analyzed by small RNA sequencing and validated by RT-qPCR, and the effects of miR-134-5p on rat Schwann cell were evaluated using mimics or inhibitors in Transwell migration, scratch-wound, and CCK-8 proliferation assays. In the PNI group, distal stumps exhibited marked edema, disruption of fiber architecture, rapid myelin breakdown, and a robust increase in CD31⁺ vascular rings, whereas compared with PNI, the SCI+PNI group showed milder edema and structural disruption, higher numbers of intact myelin rings, and increased MBP signal at days 3 and 7 together with a markedly smaller CD31⁺ area, indicating delayed Wallerian degeneration and reduced angiogenesis. Small RNA sequencing identified multiple differentially expressed miRNAs, with miR-134-5p and miR-142-5p significantly downregulated in the SCI+PNI group and this pattern confirmed by RT-qPCR; functionally, miR-134-5p overexpression enhanced Schwann cell migration and proliferation, while inhibition produced the opposite effects. These findings indicate that SCI attenuates distal nerve responses to PNI by delaying myelin clearance, impairing angiogenesis, and downregulating repair-promoting miRNAs such as miR-134-5p, suggesting that targeting miRNA-mediated Schwann cell regulation may provide new strategies to improve peripheral nerve and wound repair below the level of SCI.