Compression induces acute demyelination and potassium channel exposure in spinal cord.

Crush to the mammalian spinal cord leads to primary mechanical damage followed by a series of secondary biomolecular events. The chronic outcomes of spinal cord injuries have been well detailed in multiple previous studies. However, the initial mechanism by which constant displacement injury induces conduction block is still unclear. We therefore investigated the anatomical factors that may directly contribute to electrophysiological deficiencies in crushed cord. Ventral white matter strips from adult guinea pig spinal cord were compressed 80%, either briefly or continuously for 30 min. Immunofluorescence imaging and coherent anti-Stokes Raman spectroscopy (CARS) were used to visualize key pathological changes to ion channels and myelin. Compression caused electrophysiological deficits, including compound action potential (CAP) decline that was injury-duration-dependent. Compression further induced myelin retraction at the nodes of Ranvier. This demyelination phenomenon exposed a subclass of voltage-gated potassium channels (K(v)1.2). Application of a potassium channel blocker, 4-aminopyridine (4-AP), restored the CAP to near pre-injury levels. To further investigate the myelin detachment phenomenon, we constructed a three-dimensional finite element model (FEM) of the axon and surrounding myelin. We found that the von Mises stress was highly concentrated at the paranodal junction. Thus, the mechanism of myelin retraction may be associated with stress concentrations that cause debonding at the axoglial interface. In conclusion, our findings implicate myelin disruption and potassium channel pathophysiology as the culprits causing compression-mediated conduction block. This result highlights a potential therapeutic target for compressive spinal cord injuries.