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Infection and Immunity, September 2000, p. 5364-5376, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Immunopathology of Cerebral Malaria: Morphological Evidence of
Parasite Sequestration in Murine Brain Microvasculature
Jocelyn
Hearn,1
Neil
Rayment,1
David N.
Landon,2
David R.
Katz,1 and
J. Brian
de Souza1,*
Department of Immunology, Royal Free and
University College London Medical School, Windeyer Institute of
Medical Science, London W1P 6DB,1 and
Department of Neuropathology, Institute of Neurology,
London WC1N 3BG,2 United Kingdom
Received 13 March 2000/Returned for modification 12 May
2000/Accepted 10 June 2000
A murine model that closely resembles human cerebral malaria is
presented, in which characteristic features of parasite
sequestration and inflammation in the brain are clearly demonstrable.
"Young" (BALB/c × C57BL/6)F1 mice infected
with Plasmodium berghei (ANKA) developed typical
neurological symptoms 7 to 8 days later and then died, although their
parasitemias were below 20%. Older animals were less susceptible.
Immunohistopathology and ultrastructure demonstrated that neurological
symptoms were associated with sequestration of both parasitized
erythrocytes and leukocytes and with clogging and rupture of vessels in
both cerebral and cerebellar regions. Increases in tumor necrosis
factor alpha and CD54 expression were also present. Similar phenomena
were absent or substantially reduced in older infected but asymptomatic
animals. These findings suggest that this murine model is suitable both
for determining precise pathogenetic features of the cerebral form of
the disease and for evaluating circumventive interventions.
*
Corresponding author. Mailing address: Department of
Immunology, Royal Free and University College London Medical School, Windeyer Institute of Medical Science, 46 Cleveland Street, London W1P
6DB, United Kingdom. Phone: 44-020 7679 9354. Fax: 44-020 7679 9357. E-mail: J.deSouza{at}ucl.ac.uk.
Infection and Immunity, September 2000, p. 5364-5376, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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