The pathophysiology of chronic relapsing experimental allergic encephalomyelitis in the Lewis rat

Electrophysiological studies were performed in Lewis rats with chronic relapsing experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig spinal cord and adjuvants and treatment with low dose cyclosporin A. During clinical episodes there was conduction failure in the central nervous system (CNS), namely the spinal cord dorsal columns, and in the afferent fibres in the peripheral nervous system (PNS). The following observations indicated that the conduction failure was mainly due to demyelination-induced conduction block: (1) rate-dependent conduction block in the CNS and PNS; (2) temporal dispersion due to slowing of PNS conduction; (3) restoration of PNS conduction by cooling; (4) restoration of CNS conduction by ouabain; (5) previously demonstrated histological evidence of primary demyelination in the dorsal columns, dorsal root ganglia and dorsal roots; and (6) the temporal association of restoration of conduction with remyelination. However, it is likely that CNS and PNS axonal degeneration, which occurs in this disease, also contributed to the conduction failure. In clinical remissions there was restoration of conduction in the CNS and PNS which can be explained by ensheathment/remyelination by oligodendrocytes and Schwann cells, respectively. In most rats during clinical episodes the cerebral somatosensory evoked potential was reduced in amplitude and prolonged in latency, which can be accounted for by demyelination and axonal degeneration in the CNS and PNS components of the afferent pathway. In 2 rats with episodes of EAE, however, this potential was markedly increased in amplitude, which might have been due to demyelination-induced conduction block of descending pathways that normally inhibit synaptic transmission in the afferent pathway. In well-established remission there was residual conduction failure in the CNS and PNS which can be mainly accounted for by axonal degeneration.