# TRANSPORT OF MODIFIED ALBUMIN ACROSS BLOOD-BRAIN BARRIER

> **NIH NIH R01** · INSTITUTE FOR BASIC RES IN DEV DISABIL · 1993 · $135,056

## Abstract

The goal of this proposal is the experimental elucidation of basic
cellular mechanisms responsible for normal or abnormal function of the
blood-barrier (BBB). The main hypothesis to be tested is that
intentional modification of bovine serum albumin (BSA) molecules
increases their absorption to the surface of endothelial cells (ECs) and
consequently facilitates uptake (endocytosis) and eventual transport
(transcytosis across the wall of brain blood microvessels (capillaries,
arterioles and venules). Thus, such a modification can interfere with
the barrier function of the brain microvasculature. The albumin was
chosen as a model protein because it is one of the normal components of
blood plasma that serves as a carrier for many  important molecules and
does not affect the brain function, it can be chemically modified, and
after complexing with colloidal gold it is excellently visible by
electron microscopy (EM). Thus, it meets all requirements as a tracer
for ultrastructural study, enabling one to gain insight into cellular
mechanisms governing the function of the BBB. To test this hypothesis,
the following modified BSA compounds complexed with colloidal gold will
be used for perfusion of brain vasculature, and their interaction with
the Ecs will  be examined by EM: (1) cationized BSA, (2) poly-L-lysine-
BSA complexes, as cationic tracers acting   through coulombic forces
(attraction by anionic sites present on the EC surfaces, (3) WGA-BSA,
(4) RCA-BSA complexes acting through the affinity of a given lectin to
specific sugar residues known to be present on the EC surfaces, (5)
carbohydrate-modified albumin (glucosyl-, mannosyl-, and galactosyl-BSA)
complexes acting through affinity to specific sugar-binding molecules
(putative sugar-recognition sites or lectin-like molecules), which have
been found to be present on the surface of some non-BBB types of
endothelia but have not yet been studied in the BBB, (6) fatty acid-BSA
complexes, the uptake of which by non-BBB type of Ecs was observed to be
doubled, as compared to native BSA-gold complex.

All these experiments will be performed on normal adult mice and for
comparative purposes on aged animals and also on newborn mice with
undeveloped (immature) BBB. Scrapie-infected mice will be used as an
animal model related to aging, human neurodegenerative diseases and slow
viral infection, presumably affecting the normal function of the BBB.

These studies can shed new light on the mechanisms of delivery of
albumin-bound, pharmacologically active substances to brain parenchyma
in any pathological conditions in which it may be therapeutically
advantageous.

## Key facts

- **NIH application ID:** 3122250
- **Project number:** 5R01AG010279-02
- **Recipient organization:** INSTITUTE FOR BASIC RES IN DEV DISABIL
- **SAM.gov UEI:** LKEPMM3KKF27
- **Principal Investigator:** ANDRZEJ W VORBRODT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $135,056
- **Award type:** 5
- **Project period:** 1992-05-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122250

## Citation

> US National Institutes of Health, RePORTER application 3122250, TRANSPORT OF MODIFIED ALBUMIN ACROSS BLOOD-BRAIN BARRIER (5R01AG010279-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122250. Licensed CC0.

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