Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis.

Abstract

Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 weeks post-inoculation (PI), while several were asymptomatic up to 74 weeks PI. Two animals showed a relapsing clinical course. Examination of the spinal cords of all animals revealed chronic demyelination, remyelination, and recent demyelination. Marked perivascular inflammation, including plasma cells, was seen within demyelinated plaques. The usual type of central nervous system (CNS) remyelination was documented but in addition, remyelination of CNS axons by invading Schwann cells was noted. This Schwann cell invasion, not previously seen in EAE, was predominantly in the area of the root entry zone, and occasionally involved extensive areas of the dorsal or ventral horns. The extent of Schwann cell invasion, as well as the usual CNS-type remyelination, demonstrates the reparative capacity of the CNS. The recurrent clinical and morphologic changes in these long-term animals provides further evidence that this model of chronic EAE has many features reminiscent of multiple sclerosis. The underlying immunologic mechanisms responsible for the recurrent disease in these animals are unknown. The presence of plasma cells in the inflammatory exudates might suggest a role for B cells in these chronic animals. The possibility of an intermittent release of loculated adjuvant/antigen accounting for the recurrent disease was considered.