Remyelination of central nervous system lesions in experimental genital herpes simplex virus infection.
To study spinal cord remyelination in a model of genital herpes simplex virus type 2 (HSV-2) infection, adult female mice were inoculated by a vaginal route. At intervals up to 6 months after infection, cord tissues were removed and examined by light and electron microscopy and by immunohistochemical methods. As a consequence of acute infection, 60% of mice developed multifocal central nervous system (CNS) demyelinative lesions in the lower thoracic, lumbar, or upper sacral cord. These lesions, already present 10 days after infection, contained naked axons and mononuclear cells, including macrophages. At 2 weeks, while active myelin breakdown was still ongoing, numerous Schwann cells were present in lesions and surrounded denuded axons. At 3 weeks, the earliest remyelination was seen, and was carried out by Schwann cells and to a lesser extent by oligodendrocytes. Remyelination was extensive by 6-10 weeks and was apparently completed after 3 months. Immunocytochemical studies using antisera to myelin proteins showed relatively distinct zones of central and peripheral remyelination in some lesions, whereas remyelination was of mixed type in others. Thus the remyelinative response following experimental HSV-2-induced CNS demyelination begins promptly, proceeds briskly and goes to completion. With a natural route of inoculation and a relatively avirulent strain of this human pathogen, we have produced a model of CNS white matter injury and repair in a high proportion of infected mice that may be useful in understanding mechanisms of human demyelinative disease.
Soffer
D
D
Laboratory of Experimental Neuropathology, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Martin
J R
JR
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D006558:Herpes Genitalis / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009416:Nerve Regeneration; D013116:Spinal Cord / Q000503:physiopathology* / Q000648:ultrastructure; D013997:Time Factors