title: 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.
authors.affiliation: Department of Pharmacology, Marine Drug & Food Institute, Ocean University of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Guo
authors.forename: Xianliang
authors.initials: X
authors.lastname: Xin
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.forename: Qin
authors.initials: Q
authors.lastname: Nie
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology*; D002138:Calibration; D005260:Female; D007275:Injections, Intravenous; D008351:Mannans / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D015203:Reproducibility of Results; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D008351:Mannans; C500727:acidic oligosaccharide sugar chain, Echlonia Kurome Okam