Microscopic perfusion changes. Evans blue perfusion shows normal capillary bed network in cortex (top row) and striatum (bottom row) of Gcdh−/+ control after 72-hours of protein diet and Gcdh
−/− mice on standard diet. Note normal appearance of striatal arteries (black arrows). After 36-hours of protein diet, Gcdh
−/− mice show loss of capillary bed perfusion with continued filling of larger non-exchange vessels. Note dilated striatal arteries (black arrows) and veins (white arrows). After 48-hours of protein diet exposure, capillary bed perfusion is limited with prominence of larger non-exchange vessels. Note continuity between non-exchange vessels in cortex (arrows) and increased background signal indicating permeability (scale bars = 200 μm). Bar graph) Gcdh
−/− mouse brain samples from cortex (Ctx), striatum (Str), hippocampus (Hip) and cerebellum (Cer) were evaluated for Evans blue concentration after standard (SD) or high protein (Pro) diet compared to Gcdh
−/+ control. (± S.E.M, * p < 0.05 compared to Gcdh
−/+, # p < 0.05 compared to Gcdh
−/− SD, n = 4 per group).