In Vivo and In Vitro Models of Demyelinating Diseases

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Abstract
• Suckling rats of three inbred and three outbred strains were inoculated intraperitoneally (IP) or intracerebrally (IC) with the JHM strain of mouse hepatitis virus (JHMV) and were monitored for evidence of neurologic diseases. Consequences of varying age at inoculation, route of injection, and virus dose were ascertained. No disease was evident after IP injection but IC inoculation with at least 104 plaque-forming units at 2 days of age resulted in either a rapidly fatal encephalitis or a chronic, progressive, fatal neurologic disease in most rats, regardless of strain. Inoculation at 5 or 10 days of age predominantly caused the chronic neurologic disease, characterized by demyelinating lesions in the brain, spinal cord, or optic nerve, which sometimes were evident as late as several months postinoculation. Demyelination in the optic nerve proved to be concurrent with demyelinating lesions elsewhere in the CNS. Occasionally, clinical remissions were observed in rats in which posterior paralysis developed, suggesting that remyelination in the rat can occur. Demonstration of virus replication, by infectivity, in rats exhibiting neurologic disease and in rats without clinical symptoms was substantiated by electron microscopic observations of virus development and assembly in oligodendroglia of the optic nerve and spinal cord. In view of the protracted course of the disease in some rats, presence of demyelinating lesions confirmed by light and electron microscopy, and remissions of clinical symptoms, the JHMV-infected rat seems to be an appropriate animal model to study virusmediated progressive demyelinating disease.