Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier
Figure 5
Both ECM and hyperparasitemia are associated with upregulation of endothelial ICAM-1.
CBA/CaJ mice were infected with PbA, PyXL, or no parasites (control) and inoculated with PE-conjugated anti-ICAM-1 and Evans blue. A–D) Maximum projections of representative intravital microscopy movies showing endothelial ICAM-1 expression in postcapillary venules, and less so in arterioles (Art), in mice infected with PbA and PyXL compared to uninfected control mice. Note the pronounced ICAM-1 label along the endothelial junctions. A) PbA-infected mouse with ECM (day 6), B) PyXL-infected mouse with hyperparasitemia (day 5), C) uninfected control mouse. Note that ECM, but not hyperparasitemia, is associated with the expression of ICAM-1 on the surface of arrested leukocytes (light open circles, arrows). D) Endothelial ICAM-1 is upregulated, while ICAM-1 expressing leukocytes are absent, after FTY720 treatment of PbA-infected mice (day 9, no neurological signs). Scale bar = 20 µm. E) The endothelial ICAM-1 signal is similarly increased in cortical postcapillary venules from mice infected with PbA and PyXL compared to uninfected control mice. ICAM-1 is significantly upregulated in cortical arterioles during both ECM and hyperparasitemia compared to uninfected control mice. Compared to postcapillary venules, however, the overall level of ICAM-1 expression in arterioles is significantly lower. F) ICAM-1 fluorescence emission of individual leukocytes (N = 6) is higher during ECM compared to hyperparasitemia. G) The density of ICAM-1 expressing leukocytes in postcapillary venules from mice with ECM is significantly higher compared to mice with hyperparasitemia. Significance (*, P<0.05; **, P<0.01) was determined with 1-way ANOVA followed by Tukey's test for multiple comparisons. See Table S13 for details and Videos S17–S19 for the corresponding dynamic data.