Figure 3.

Selective tight junction breakdown leads to blood–brain barrier leakage. Staining of tight junctions [zona occludens 1 (ZO-1), green], immunoglobulin (red), and von Willebrand Factor (blue) in (A) normal controls, (B) epileptic controls, and (C–G) FEPSO cats positive for LGI1 antibodies. The tight junction protein ZO-1 is found between endothelial cells in a strong and (in longitudinal cuts) continuous staining in (A) normal controls in the hippocampus. Therefore, weak immunoglobulin staining is restricted to the luminal side of the blood vessels. (B) In hippocampi of epileptic controls, the ZO-1 staining is weaker, less continuous, and associated with some immunoglobulin reactivity in the parenchyma. (C) In FEPSO, blood vessels in the hippocampus have very weak and discontinuous ZO-1 signal, indicating tight junction breakdown. Here, immunoglobulin has clearly leaked into the parenchyma. (D) In the amygdala, the same pattern of tight junction breakdown was seen, indicated by a weak and discontinuous ZO-1 staining, and immunoglobulin leakage into the parenchyma. In all other investigated brain areas such as (E) basal ganglia, (F) cortex, and (G) cerebellum, in FEPSO cats, no ZO-1 breakdown was observed and immunoglobulin only was found on the luminal side of the vessels or perivascular space. Scale bars correspond to 10 µm (A–D,F,G) or 5 µm (E).