EFFECTS OF ENDOTOXIN AND DEXAMETHASONE ON CEREBRAL MALARIA IN MICE

CBA/T6 and DBA/2J mice inoculated with Plasmodium berghei ANKA (PbA) d evelop 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 agai n within 48 h, reduced the cerebral symptoms and prevented death from cerebral malaria. Plasma tumour necrosis factor (TNF) levels, which in creased at the time of the cerebral symptoms, were also reduced in the se DXM-treated mice. Intravenously administered Evans Blue, a dye whic h binds to albumin, diffused extensively across the blood-brain barrie r only during the period of cerebral symptoms, in proportion to the se verity of the cerebral symptoms and the disease. In PbA-infected CBA m ice, cerebral symptoms and the amount of Evans Blue diffusing into the brain tissue were both reduced by DSM treatment, bur only if the ster oid was given on day 3 and again within 48 h. Endotoxin injected intra vascularly into PbA-infected DBA mice after day 5 resulted in an exagg eration of cerebral symptoms and death between days 6 and 9. Plasma TN F and the amount of Evans Blue in the brain parenchyma increased above normal levels in these mice. Endotoxin injections had only minor effe cts on the severity of the cerebral symptoms in PbA-infected CBA mice and did not cause the animals to die sooner.