DEMYELINATION IN SEVERE COMBINED IMMUNODEFICIENT, MICE BY INTRACISTERNAL INJECTION OF CEREBROSPINAL-FLUID CELLS FROM PATIENTS WITH MULTIPLE-SCLEROSIS - NEUROPATHOLOGICAL INVESTIGATION
H. Fujimura et al., DEMYELINATION IN SEVERE COMBINED IMMUNODEFICIENT, MICE BY INTRACISTERNAL INJECTION OF CEREBROSPINAL-FLUID CELLS FROM PATIENTS WITH MULTIPLE-SCLEROSIS - NEUROPATHOLOGICAL INVESTIGATION, Acta Neuropathologica, 93(6), 1997, pp. 567-578
Demyelinating lesions have been observed in severe combined immunodefi
cient (SCID) mice after intracisternal administration of cerebrospinal
fluid cells (CSFC) from patients with multiple sclerosis (MS). Furthe
r investigation in our laboratory revealed that CSFC from 6 of 15 pati
ents at exacerbation of MS caused demyelination. The factor leading to
demyelination appears to be the high frequency of relapses during a s
hort period, but not the severity of the disease. Neuropathological an
d immunohistochemical studies revealed that a lack of inflammatory mon
onuclear 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 i
ntracisternal administration of CSFC, foamy/vacuolar lesions with a sm
all or moderate number of lipid-laden macrophages were seen in the whi
te mater. Ultrastructurally, relative preservation of axons, in contra
st 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 w
ith poor remyelination were seen. The findings were similar to those s
een in experimental allergic encephalomyelitis, though without lymphoc
ytic infiltration, but were quite different from the lesions observed
in Theiler's murine encephalitis virus infection. The absence of an im
munohistochemical reaction to the human leukocyte common antigen in th
e infiltrating mononuclear cells suggested that the graft-versus-host
reaction was an unlikely cause of the demyelinating lesions.