Restore axonal conductance in a locally demyelinated axon with electromagnetic stimulation

<i>Objective</i>. Axonal demyelination leads to failure of axonal conduction. Current research on demyelination focuses on the promotion of remyelination. Electromagnetic stimulation is widely used to promote neural activity. We hypothesized that electromagnetic stimulation of the demyelinated area, by providing excitation to the nodes of Ranvier, could rescue locally demyelinated axons from conductance failure.<i>Approach</i>. We built a multi-compartment NEURON model of a myelinated axon under electromagnetic stimulation. We simulated the action potential (AP) propagation and observed conductance failure when local demyelination occurred. Conductance failure was due to current leakage and a lack of activation of the nodes in the demyelinated region. To investigate the effects of electromagnetic stimulation on locally demyelinated axons, we positioned a miniature coil next to the affected area to activate nodes in the demyelinated region.<i>Main results</i>. Subthreshold microcoil stimulation caused depolarization of node membranes. This depolarization, in combination with membrane depolarization induced by the invading AP, resulted in sufficient activation of nodes in the demyelinated region and restoration of axonal conductance. Efficacy of restoration was dependent on the amplitude and frequency of the stimuli, and the location of the microcoil relative to the targeted nodes. The restored axonal conductance was due to the enhanced Na⁺current and reduced K⁺current in the nodes, rather than a reduction in leakage current in the demyelinated region. Finally, we found that microcoil stimulation had no effect on axonal conductance in healthy, myelinated axons.<i>Significance</i>. Activation of nodes in the demyelinated region using electromagnetic stimulation provides an alternative treatment strategy to restore axonal function under local demyelination conditions. Results provide insights to the development of microcoil technology for the treatment of focal segmental demyelination cases, such as neuropraxia, spinal cord injury, and auditory nerve demyelination.