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Effects of endotoxin and dexamethasone on cerebral malaria in mice

Published online by Cambridge University Press:  06 April 2009

A. L. Neill  and
N. H. Hunt
A. L. Neill
Affiliation:
Department of Pathology, University of Sydney, N.S.W. 2006, Australia
N. H. Hunt
Affiliation:
Department of Pathology, University of Sydney, N.S.W. 2006, Australia
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Summary

CBA/T6 and DBA/2J mice inoculated with Plasmodium berghei ANKA (PbA) develop cerebral involvement 6–8 days post-inoculation, from which the CBA mice almost invariably die and the DBA mice recover. Dexamethasone (DXM; 80 mg/kg) given to inoculated CBA mice twice, on day 3 and again within 48 h, reduced the cerebral symptoms and prevented death from cerebral malaria. Plasma tumour necrosis factor (TNF) levels, which increased at the time of the cerebral symptoms, were also reduced in these DXM-treated mice. Intravenously administered Evans Blue, a dye which binds to albumin, diffused extensively across the blood-brain barrier only during the period of cerebral symptoms, in proportion to the severity of the cerebral symptoms and the disease. In PbA-infected CBA mice, cerebral symptoms and the amount of Evans Blue diffusing into the brain tissue were both reduced by DXM treatment, but only if the steroid was given on day 3 and again within 48 h. Endotoxin injected intravascularly into PbA-infected DBA mice after day 5 resulted in an exaggeration of cerebral symptoms and death between days 6 and 9. Plasma TNF and the amount of Evans Blue in the brain parenchyma increased above normal levels in these mice. Endotoxin injections had only minor effects on the severity of the cerebral symptoms in PbA-infected CBA mice and did not cause the animals to die sooner.

Keywords

dexamethasoneendotoxincerebral malariablood-brain barriertumour necrosis factor
Type
Research Article
Information
Parasitology , Volume 111 , Issue 4 , November 1995 , pp. 443 - 454
Copyright
Copyright © Cambridge University Press 1995

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