Aspects of the pathogenesis and neuropathology of louping-ill
encephalitis have been investigated in rodents and sheep.
In animals inoculated intraperitoneally virus was detected in the
circulation before being isolated from nervous tissue. There was, however,
no indication as to the means by which virus particles passed from blood to
brain. Replication of virus within the central nervous system appeared to
be confined to the cytoplasm of nerve cells. In infant hamster cerebellum
virions were found within abnormal cytoplasmic membranes in both Purkinje
cells and granule cells. Neurons containing these membranes were depleted
of granular endoplasmic reticulum and showed loss of Nissl substance.
Chromatolysis was seen also in ventral horn cells of moribund sheep but,
although viral antigen was demonstrated in the majority of such cells by
immunofluorescence, virus particles were not found on ultrastructural
examination. Necrosis of ventral horn cells in sheep was accompanied by
diminution in acid phosphatase activity and fragmentation of the Golgi
Onset of symptoms preceded obvious neuronal loss in 75 per cent, of
C57 black mice inoculated intraperitoneally. However in most other
experiments nerve cell necrosis could be correlated with neurological
dysfunction. In infant hamsters and moribund sheep the distribution patterns
of neuronal damage and cells containing virus particles and viral antigen
were similar. It is concluded that the basic cause of louping-ill is damage
of nerve cells by the virus.
Neuronal damage in moribund sheep was most apparent in the vestibular
nuclei, the motor nuclei, the Purkinje cells of the cerebellum and the ventral horns of the spinal cord. The telencephalon was relativelyunaffected.
This distribution of lesions was seen in animals that were
inoculated intracerebrally or subcutaneuosly, and in natural cases.
Neuropathological changes were more generalized in mice inoculated intra¬
cerebrally, and were not obviously affected either by the strain of host or
the presence of concurrent lesions of scrapie. Severe neuron necrosis was
seen in infant hamsters and rats, but not in those more than 14 days old at
inoculation. In sheep, however, the severity of lesions was similar in all
age groups. No general principle can be formulated to explain the
distribution of virus infected nerve cells in animals with louping-ill.
Virus was detected in nervous tissue before inflammatory changes were
apparent. Severe neuron necrosis was seen in all moribund sheep, and
inflammatory changes were most marked in those with the longest incubation
times. There were slight generalized inflammatory lesions, which were
either perivascular or associated with effete neurons, in all surviving
sheep and in subclinically affected hamsters and rats. Inflammation is
essentially a secondary phenomenon, which occurs after nerve cells are
infected with virus.
The perivascular cuff was studied intensively in moribund sheep.
Histologically most constituents of the cuff appeared to be of the lymphoid
type, with a few classical plasma cells and monocytes. The majority were
shown to contain globulin in their cytoplasm, when stained with a fluorescent
conjugate prepared against sheep IgG. Electron microscopy showed that most
of the perivascular inflammatory cells were plasmacytes. Infiltrating cells
were also seen to be of the plasma cell type and were observed to enter nervous tissue without causing any obvious damage to either endothelial
cells or their basement membranes. Thus perivascular cuffing in sheep with
louping-ill results mainly from migration of circulating plasma cells, or
plasma cell precursors, into the central nervous system and is a specific
response to the presence of viral antigen in the tissues. The inflammatory
reaction is a protective mechanism, and is not responsible for the
development of symptoms. In this respect it is unlike the histologically
similar delayed allergic reaction.