The relationship of astrocytes and macrophages to CNS demyelination after experimental herpes simplex virus infection

Abstract

Corneal inoculation of mice with herpes simplex virus type I (HSV) produces central nervous system (CNS) demyelination 7 to 8 days after infection. The demyelination originates at the junction between PNS and CNS in the trigeminal root entry zone. The pathogenesis for this selective demyelination is unknown. Immunosuppression with cyclophosphamide reduces the extent of demyelination, but does not eliminate the lesion entirely. This report concerns the electron microscopic evaluation of the events preceding demyelination. The astrocytes forming the CNS junction are heavily infected 62 hours after corneal inoculation before myelin breakdown. These cells then undergo lysis, releasing viral and cellular debris. Perivascular monocytes appear in the CNS at this time, and proceed to phagocytize the dying cells. These monocytes may be important in transferring antigenic information to the cell-mediated immune system, which responds by producing extensive CNS demyelination by 6 to 7 days postinfection.