COMPARISONS BETWEEN MICROVASCULAR CHANGES IN CEREBRAL AND NONCEREBRALMALARIA IN MICE, USING THE RETINAL WHOLE-MOUNT TECHNIQUE

CBA/T6 mice inoculated with Plasmodium berghei ANKA strain (PbA) exhib ited cerebral symptoms and died from cerebral malaria 6-8 days p.i. wh ereas DBA/2J mice developed (around days 6-9) a non-fatal cerebral mal aria, with milder cerebral symptoms, and died between days 15 and 22 f rom other malaria-related complications. When inoculated with P. bergh ei K173 (Pb) these mouse strains did not develop cerebral malaria. The se mouse/parasite strain combinations were used, in conjunction with t he retinal whole-mount technique, to elucidate factors critical in the pathology of murine cerebral malaria. CBA/T6 mice infected with PbA ( PbA-CBA mice) demonstrated mild changes in vascular permeability as ea rly as days 2-3, prior to the appearance on day 5 of cerebral symptoms , whereas mice with non-cerebral malaria did not show any vascular per meability changes until the very late stage of the disease (days 14-22 ). In the PbA infections, progressive deterioration of endothelial bar rier properties, demonstrated by Evans' Blue leakage both generally an d from specific focal areas, as well as a developing monocytosis and a dherence of mononuclear cells to the endothelium of the retinal vessel s continued until death (in CBA/T6 mice) or resolution (in DBA/2J mice ). Adherent monocytes, particularly in PbA-CBA mice, were associated w ith reduced Hoechst staining of individual endothelial cells and a ban king up proximally of both parasitized and non-parasitized blood cells in the small blood vessels, often with accompanying focal leakage of Evans' Blue from the retinal vessels. The occurrence and severity of t hese early changes in the microcirculation correlated with the subsequ ent development of cerebral symptoms. Monocyte margination appeared to be the most significant factor associated with the development of cer ebral symptoms.