IMMUNOCYTOCHEMICAL EVALUATION OF BLOOD-BRAIN-BARRIER TO ENDOGENOUS ALBUMIN IN SCRAPIE-INFECTED MICE

A quantitative immunocytochemical procedure was used for evaluation of the blood-brain barrier (BBB) to endogenous albumin in plaque-forming (PF) and non-plaque-forming (NPF) groups of scrapie-infected mice at the clinical stage of disease. Ultrathin sections of brain samples (ce rebral cortex, hippocampus and cerebellum) embedded in resin (Lowicryl K4M) were exposed to anti-mouse albumin antiserum followed by protein A-gold. Using morphometry, the density of immunosignals (gold particl es per mu m(2)) was recorded over four compartments: vascular lumen, e ndothelium, subendothelial space, and brain parenchyma (neuropil). Mor phometric and statistical analyses did not reveal significant differen ces in the barrier function of the microvasculature of the cerebral co rtex and hippocampus in either group of mice, although a slight increa se in the number of leaking vessels in the PF group was noted. In cont rast, in the cerebellum, the permeability of the microvessels to album in was significantly higher in the PF than in the NPF mouse group, and this was paralleled by the infiltration of the walls of numerous vasc ular profiles with amyloid deposits (amyloid angiopathy). These data a lso indicate the existence of distinct regional differences in BBB fun ction in the brain of scrapie-infected mice. The vascular amyloid depo sits and the amyloid plaques present in the cerebral cortex of PF mice were labeled with numerous immunosignals suggesting the affinity of e xtravasated albumin to these deposits. In conclusion, no convincing ev idence was obtained indicating that impairment of the BBB, manifested by increased permeability of vascular segments, is directly related to the deposition of amyloid in the vascular wall and in plaques. Segmen tal impairment of the barrier function seems to be rather the result o f disturbed structural integrity of the components of the vascular wal l.