PATTERNS OF OLIGODENDROCYTE PATHOLOGY IN CORONAVIRUS-INDUCED SUBACUTEDEMYELINATING ENCEPHALOMYELITIS IN THE LEWIS RAT

Intracerebral infection of rats with JHM coronavirus induces a chronic inflammatory demyelinating disease, which in many respects mimicks th e pathology of multiple sclerosis. We investigated the patterns of dem yelination and oligodendrocyte pathology in this model. In early stage s of the disease infection of oligodendrocytes was associated with a d ownregulation of expression of mRNA for proteolipid protein in the abs ence of myelin destruction. When demyelinating lesions were formed inf ected oligodendrocytes were destroyed by necrosis, whereas oligodendro cytes that did not contain detectable virus antigen or RNA were in par t dying by apoptosis. At this stage of the disease remyelination of th e lesions was pronounced. At later stages after infection virus antige n was nearly completely cleared from the lesions. In spite of the lack of detectable virus, ongoing demyelination and unspecific tissue dest ruction occurred, and oligodendrocytes were mainly destroyed by apopto sis. These late lesions revealed only minimal central remyelination, b ut they were frequently repaired by Schwann cells. Our studies suggest that the mechanisms of myelin destruction in this model of virus-indu ced demyelination are complex and that the patterns of tissue damage m ay change during the course of the disease. (C) 1997 Wiley-Liss, Inc.