Ultrastructural study on the interaction of native and cationized albumin-gold complexes with mouse brain microvascular endothelium.
The main objective of this ultrastructural study was to gain insights into the cellular mechanisms responsible for the enhanced brain uptake of blood-borne cationized albumin observed by several authors utilizing quantitative methodology. Mice were injected intravenously or into the common carotid artery (in vivo experiments) or perfused in situ with solutions of native or cationized bovine serum albumin complexed with colloidal gold (BSA-G or cBSA-G respectively). The results indicate that: (1) the main drawbacks of in vivo experiments are very intense phagocytosis of the tracer particles by Kupffer cells located in the liver sinusoids and also escape of the tracer through capillaries of skeletal and heart muscles. This results in a rapid decline of the concentration and disappearance of the circulating tracer particles; (2) BSA-G and cBSA-G both in vivo (up to 30 min circulation) or after perfusion in situ (up to 15 min) do not cross the wall of brain microvessels representing the blood-brain barrier; (3) enhanced entrance of cationized albumin into the brain occurs through fenestrated endothelium of the capillaries located in the examined circumventricular organs (median eminence and neurohypophysis). Although BSA-G is also transported by these fenestrated capillaries, this process is evidently less intense than in the case of cBSA-G; (4) the enhanced passage of cBSA-G across fenestrated capillaries occurs mainly via vesicular transport (adsorptive transcytosis), through transendothelial channels and eventually through interendothelial junctional clefts; (5) the fenestrated capillaries of the choroid plexus appear to be less permeable for both tracers than those located in the other circumventricular organs.
Vorbrodt
A W
AW
New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Dobrogowska
D H
DH
Lossinsky
A S
AS
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000166:cytology; D002339:Carotid Arteries; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010477:Perfusion; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D012710:Serum Albumin, Bovine; D006046:Gold