Figure 1. Model for C3a-mediated neurovascular inflammation and BBB permeability.
Top: With age, C3aR-mediated endothelial cell VCAM1 expression increases in the cortex and hippocampus and VE-cadherin is downregulated. Subsequent endothelial cell calcium (Ca2+) release disrupts tight junctions, which increases BBB permeability. RBCs, plasma proteins, and leukocytes can infiltrate the vasculature where they can adhere, roll, and then leak into extravascular tissue. Bottom: Propson et al. (6) showed that treatment with a C3aR antagonist blocked C3a from binding to C3aRs, preventing pathological changes in tight junctions and subsequent leukocyte extravasation.