Ultrastructural and permeability features of microvessels in the hippocampus, cerebellum and pens of senescence-accelerated mice (SAM)

We previously reported that the accumulation of blood-borne radiolabelled s erum albumin in brain parenchyma increased with aging, especially in senesc ence-accelerated mice (SAMP8), which showed age-related deficits in learnin g and memory. In this study, in order to examine morphological events relat ed to the age-related increase of the brain accumulation of serum albumin, the transvascular passage of blood-borne horseradish peroxidase (HRP) and u ltrastructural features of microvessels were examined in the hippocampus, c erebellum and pens of SAMP8 and SAMR1 (control) mice. Ultrastructural exami nation of the hippocampus showed that the staining for HRP was occasionally spreading throughout the parajunctional cytoplasm of the endothelial cell of aged SAMP8 mice, but not in young SAMP8 mice nor in SAMR1 mice. The numb er of vessels showing the staining reaction for HRP in the parajunctional c ytoplasm of the endothelial cells in aged SAMP8 mice increased significantl y compared with that in the others. Electron microscopic morphometry showed that there were no significant differences among the number of HRP-positiv e vesicles per unit area of the endothelial cell cytoplasm in young and old mice of both strains. The staining reaction for HRP was not seen in the ba sal lamina of microvessels and the perivascular neuropil in all mice examin ed. Perivascular lipofuscin-like granules and collagen deposits, swelling o f astroglial perivascular endfeet and perivascular cells containing foamy, lipid-like droplets were frequently found in several brain regions of aged SAMP8 mice. The perivascular cells with a few lipid-like droplets and more electron-homogenous lysosomes were occasionally seen in SAMR1 and young SAM P8, while the other findings were scarcely observed in SAMR1 and young SAMP 8 mice. These findings suggest that the blood-brain barrier to HRP was preserved in microvessels in three brain regions of SAM mice but the blood microvessels showed some age-related ultrastructural alterations in SAMP8 brains. Uncon trolled passage of HRP through the parajunctional cytoplasm of the endothel ial cells may partly contribute to the age-related increase of accumulation of serum albumin in SAMP8 brains. (C) 2001 Elsevier Science Inc. All right s reserved.