Determination of the accessibility of acidic oligosaccharide sugar chain to blood-brain barrier using surface plasmon resonance.

Abstract:

:There exist limitations in the detection of exogenous oligosaccharides due to their polydisperse and diversiform nature, and particularly the interference of endogenous glycosaminoglycans (GAGs). Herein, a surface plasmon resonance (SPR) assay for detecting acidic oligosaccharide sugar chain (AOSC), an anti-Alzheimer's drug candidate, in cerebrospinal fluid (CSF) was developed based on a carbohydrate antigen-antibody interaction. Rabbits were treated with AOSC intravenously and orally at 40 or 200 mg x kg(-1), respectively. CSF samples were collected at given time points for quantitative determination of AOSC concentrations in the CSF using an SPR-based competitive inhibition assay, and the existence of AOSC in the CSF was indicated as a blood-brain barrier (BBB) accessibility index. AOSC concentration as low as 50 ppb (0.05 microg x ml(-1)) was detected in the CSF, with its peak value approaching 2.091 and 3.316 microg x ml(-1) following intravenous and oral administration, respectively. This is the first time the capacity of AOSC to pass through the BBB has been confirmed using SPR-based competitive inhibition immunoassay. Importantly, the accessibility of AOSC to the BBB indicates AOSC has potential therapeutic value for treating neurodegenerative diseases, particular Alzheimer's disease.

journal_name

Biol Pharm Bull

authors

Guo X,Xin X,Gan L,Nie Q,Geng M

doi

10.1248/bpb.29.60

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

60-3

issue

1

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/29.60

journal_volume

29

pub_type

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