Effects of IDPN-induced axonal swellings on conduction in motor nerve fibers

Paranodal demyelination produces a reduction of conduction velocity and conduction block. The relative proportions of these changes appear to vary among different demyelinating disorders. In this study we have examined the effects on conduction of paranodal demyelination produced by giant axonal swellings. The axonal swellings were induced in rats by administration of beta, beta'-iminodipropionitrile (IDPN). In this experimental model synchronous axonal swellings occur in the proximal region of virtually every alpha-motorneuron without evidence of segmental demyelination or fiber loss. Conduction across the motor neuron was evaluated by two methods: a monosynaptic reflex pathway and intracellular recording from single motor neurons. Increases in the delay across the central region of the monosynaptic reflex pathway began between 2 and 4 days after toxin administration. Intracellular studies confirmed that the slowing occurred across the proximal regions of the motor axons; more distal regions of the motor axons were unaffected. The substantial reduction in conduction velocity over the swollen segment occurs with only moderate evidence of conduction block, as assayed by a reduction in the H-reflex/M-response amplitude ratio. Parallel morphological studies showed that in the enlarged fibers the myelin terminal loops maintained contact with the axon but were displaced from the paranodal region into the internode. The appearance of this "passive" paranodal demyelination correlated closely with the increase in conduction delay. We suggest that the contact maintained by the displaced myelin terminal loops with the axolemma allows saltatory conduction to continue, and explains the paucity of conduction block in this model despite the prominent conduction slowing.