Demyelination in severe combined immunodeficient mice by intracisternal injection of cerebrospinal fluid cells from patients with multiple sclerosis: neuropathological investigation.

Abstract

Demyelinating lesions have been observed in severe combined immunodeficient (SCID) mice after intracisternal administration of cerebrospinal fluid cells (CSFC) from patients with multiple sclerosis (MS). Further investigation in our laboratory revealed that CSFC from 6 to 15 patients at exacerbation of MS caused demyelination. The factor leading to demyelination appears to be the high frequency of relapses during a short period, but not to the severity of the disease. Neuropathological and immunohistochemical studies revealed that a lack of inflammatory mononuclear cell infiltration within and around the demyelinating lesions or in leptomeninges was a common characteristic in all SCID mice with CSFC-induced demyelination. In affected mice killed 2-3 weeks after intracisternal administration of CSFC, foamy/vacuolar lesions with a small or moderate number of lipid-laden macrophages were seen in the white matter. Ultrastructurally, relative preservation of axons, in contrast to myelinoclastic features, as well as some remyelinated axons were observed. In affected SCID mice killed 4-6 weeks after intracisternal administration, more widespread foamy macrophages and necrotic foci with poor remyelination were seen. The findings were similar to those seen in experimental allergic encephalomyelitis, though without lymphocytic infiltration, but were quite different from the lesions observed in Theiler's murine encephalitis virus infection. The absence of an immunohistochemical reaction to the human leukocyte common antigen in the infiltrating mononuclear cells suggested that the graft-versus-host reaction was unlikely cause of the demyelinating lesions.