ULTRASTRUCTURAL-STUDY OF THE CLEARANCE OF INTRACEREBRALLY INFUSED NATIVE AND MODIFIED ALBUMIN-GOLD COMPLEXES

The main objective of this ultrastructural study was to gain a better understanding of the involvement of brain vasculature in clearance of proteins from edematous fluid. For this purpose, both native and modif ied (cationized, glucosylated, and mannosylated) bovine serum albumin- gold complexes (BSA-G, catBSA-G, glucBSA-G and manBSA-G respectively) dissolved in phosphate-buffered saline (PBS) were infused (10 mu l) in to mouse cerebral cortex. Samples of brain were taken at 30 min, 1 h, and 24 h post-infusion for electron microscopical examination. All BSA -G complexes were rapidly taken up and deposited inside the cytoplasm of pericytes and of various glial cells (microglia and eventually astr ocytes) located in the area adjacent to the infusion site. Only glucBS A-G particles also appeared inside the nuclei of some cells. In the ap plied experimental conditions and at the examined time intervals, neit her BSA-G nor catBSA-G and glucBSA-G complexes were transported back t o the bloodstream, although they entered vascular basement membrane an d were eventually internalized in the endosomes or multivesicular bodi es of the endothelial cells. Only a few gold particles representing th e manBSA-G complex were found inside the vascular lumen, suggesting th eir reverse transport to a rather small degree. The mechanism of this transport, however, remains unclear. Complexes of catBSA-G were appare ntly trapped by the negatively charged vascular basement membrane and remained in this structure without any further significant uptake by t he endothelial cells. These observations suggest that large size and m ultimeric nature of albumin-gold complexes are limiting factors making it difficult to interpret the results and hampering their relevance t o the clearance in vivo of native albumin from brain edematous fluid.