Figure 7.

Diagram to illustrate the possible mechanism by which immune complexes disrupt the perivascular drainage of solutes. In (a), soluble antigen in the extracellular space interacts with IgG extravasated from the circulation resulting in immune complex formation and fixation of complement C3. The immune complexes formed block the arterial basement membranes that represent the perivascular drainage pathway. In (b), the drainage of a soluble tracer (dextran) is blocked by the presence of immune complexes in the arterial basement membranes. Alternatively, dextran is taken up by activated macrophages and microglia surrounding the blood vessels. We previously showed that macrophages/microglia are activated by FcR ligation following immune complex formation, which initiates an inflammatory in response surrounding the blood vessels (veins). The activated macrophages take up dextran by phagocytosis, thereby indirectly impeding elimination of solutes from the brain.