Degeneration and regeneration in rabbit peripheral nerve with long-term nerve cuff electrode implant: a stereological study of myelinated and unmyelinated axons

Selective and dynamically co-ordinated functional electrical stimulation (FES) of paralysed/paretic limbs in upper motor neuron lesioned people depends on optimal contact at the neural interface. Implanted nerve cuff electrodes may form a stable electrical neural interface, but may also inflict nerve damage. In this study the immediate and long-term effects of cuff implantation on the number and sizes of myelinated and unmyelinated axons have been evaluated with unbiased stereological techniques. Cuff electrodes were implanted in rabbit tibial nerves just below the knee joint, and the stereological analyses were carried out 2 weeks and 16 months after implantation. Myelinated axons were analysed at standardised levels proximal to, underneath, and distal to the cuff; unmyelinated axons underneath the cuff. A 27% loss of myelinated axons was found underneath and distal to the nerve cuff 2 weeks post surgery. All axonal sizes were equally lost except for the very smallest. At 16 months post surgery the number of myelinated axons was restored to control values at both levels. Except for the presence of regenerative sprouts at 2 weeks post surgery, no changes in the number or sizes of unmyelinated axons were revealed at either 2 weeks or 16 months post surgery. Our study demonstrates that implanted cuff electrodes may cause an initial loss of myelinated axons but with subsequent regeneration.