Ultrastructural study of the clearance of intracerebrally infused native and modified albumin-gold complexes

D.H. Dobrogowska1, A.S. Lossinsky2 and A.W. Vorbrodt1

1New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island, New York and 2Huntington Medical Research Institutes, Neurological Research Laboratories, Pasadena, USA

Offprint requests to: A.W. Vorbrodt, New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA. FAX: 719-982-6346.

Summary. 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 modified (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 µl) into 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 astrocytes) located in the area adjacent to the infusion site. Only glucBSA-G particles also appeared inside the nuclei of some cells. In the applied experimental conditions and at the examined time intervals, neither BSA-G nor catBSA-G and glucBSA-G complexes were transported back to the bloodstream, although they entered vascular basement membrane and were eventually internalized in the endosomes or multivesicular bodies of the endothelial cells. Only a few gold particles representing the manBSA-G complex were found inside the vascular lumen, suggesting their reverse transport to a rather small degree. The mechanism of this transport, however, remains unclear. Complexes of catBSA-G were apparently trapped by the negatively charged vascular basement membrane and remained in this structure without any further significant uptake by the endothelial cells. These observations suggest that large size and multimeric nature of albumin-gold complexes are limiting factors making it difficult to interpret the results and hampering their relevance to the clearance in vivo of native albumin from brain edematous fluid. Histol. Histopathol. 13, 647-656 (1998)

Key words: Intracerebral infusion, Clearance of albumin, Albumin-gold complex, Reverse transport, Blood-brain barrier

DOI: 10.14670/HH-13.647