Plasmodium berghei: Cerebral malaria in CBA mice is not clearly related toplasma TNF levels or intensity of histopathological changes

Plasmodium berghei ANKA infection in CBA/J mice leads to the development of cerebral malaria (CM) that kills 80-90% of the animals in 6-9 days. This m odel has been used to study the pathogenesis of CM, which is a major cause of morbidity and mortality in Plasmodium falciparum-infected individuals. T he role of cytokines in the induction of CM in the murine model has been we ll documented, but most studies have been restricted to the peak of neurolo gical manifestations. Here we used a sequential approach to compare mice th at developed CM with those that developed no cerebral pathology. Animals we re examined for systemic histopathological changes and plasma Tumor Necrosi s Factor-alpha (TNF) levels. The objectives were (a) to further determine t he importance of factors commonly associated with murine CM-such as elevate d levels of TNF and the presence of hemorrhage and vascular plugging-by com paring mice at different stages of infection and/or with different outcomes following infection and (b) to examine the importance of systemic changes- course of parasitemia and histopathological alterations in brain, liver, an d lungs-in the development of CM. The data suggest that (a) the clinical ma nifestation of CM appears to be associated with a wave of merozoite release on days 6-7, (b) murine CM does not present reliable histopathological ind icators, (c) there is no topographic association between the occurrence Of intravascular plugging and the hemorrhagic foci, (d) monocyte-monocyte and monocyte-endothelial cell adherence were the most expressive histopathologi cal events and were not restricted to brain vessels, (e) blood levels of TN F are not indicative of the local tissue reaction, (f) adhesiveness of mono cyte/endothelial cells fluctuate during infection and is dissociated from t he lymphocyte homing to the liver, and (g) pulmonary megakaryocytosis megak aryopoiesis?) is a late event in the lungs.