The disruption of axonal continuity and neuronal loss at the injury site leads to structural disconnections as well as functional consequences in spinal cord injury. Herkinorin, a structurally unique non-nitrogenous opioid receptor agonist, demonstrates significant neuroprotective efficacy in models of ischemic brain injury and epilepsy. In this report, we aimed to explore the role and underlying mechanism of Herkinorin in axon regeneration and functional recovery in SCI. Oxygen-glucose deprivation and restoration (OGD/R) condition was used in cell line rat pheochromocytoma cells (PC12) and primary cortical neurons to mimic SCI context in vitro. and apoptosis of the cells were detected. A rat SCI model was conducted by Allen's impactor. Cells were treated with Herkinorin under OGD/R condition. Footprint analysis and BBB scale was to evaluate locomotor function. Western blot and immunofluorescence staining of proteins Map2, GAP43 and Ace-tubulin to assess microtubule stabilization and Bax, Bad, Bcl2 as well as cleaved caspase3 to detect apoptosis. The TNFα was employed to determine the expression profiles of NF-κB. Herkinorin alleviated OGD/R-induced neuronal apoptosis and axonal damage in PC12 cells and primary neurons by enhancing microtubule stability and inhibiting NF-κB, effects abolished by TNFα. Crucially, in a rat SCI model, Herkinorin improved locomotor function (BBB scores, gait) and mitigated spinal cord neuronal loss and microtubule disassembly. Herkinorin confers neuroprotection and pro-regenerative effects against neuronal injury both in vitro and in vivo, mechanistically linked to microtubule stabilization and NF-κB pathway suppression, positioning it as a promising candidate for SCI therapy.
Wang et al. (Mon,) studied this question.