Divergent cellular responses to sciatic nerve crush versus transection: bilateral MYCN induction and distinct DRG neuronal responses.

Introduction: Peripheral nerve injuries can produce regenerative or persistent-disconnection outcomes depending on the injury modality, but the underlying cellular responses and their effects on the central nervous system remain incompletely defined. Methods: We compared sciatic nerve crush (SNC; axonotmesis) and sciatic nerve transection (SNT; neurotmesis) in wild-type, AdvCre;Ai14, and MYCN-eGFP reporter mice. Longitudinal assessments included functional recovery, neuronal injury responses marked by ATF3, IB4-positive sensory-neuron responses, dorsal-horn microglial activation, and spinal MYCN-eGFP signal. Results: SNC was associated with partial, measure-specific functional recovery, a transient and self-limited ATF3 response, and a limited reduction in IB4-positive neuronal profiles. In contrast, SNT produced persistent axotomy-associated neuronal stress, a reduction in IB4-positive neuronal profiles, and more protracted dorsal-horn microglial activation. MYCN-eGFP intensity was significantly increased above sham levels bilaterally in spinal ventral-horn neurons after both SNC and SNT at postoperative day 7 (POD7), with the greatest acute amplitude observed after SNC. From POD7 to POD14, MYCN-eGFP intensity declined by more than 90% after SNC but by approximately 60% after SNT, indicating distinct temporal patterns between the two injury modalities. Discussion: SNC and SNT engage overlapping but quantitatively and temporally distinct cellular programs, including modality-specific dorsal root ganglion neuronal responses associated with functional recovery. These findings refine the interpretation of two widely used peripheral nerve injury models and identify bilateral spinal MYCN-eGFP dynamics as a candidate cellular readout for future mechanistic investigation.