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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2011

Open Access 01-12-2011 | Research

Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole

Authors: Shin-ichi Akanuma, Yasuo Uchida, Sumio Ohtsuki, Masanori Tachikawa, Tetsuya Terasaki, Ken-ichi Hosoya

Published in: Fluids and Barriers of the CNS | Issue 1/2011

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Abstract

Background

Peripheral administration of lipopolysaccharide (LPS) induces inflammation and increases cerebral prostaglandin E2 (PGE2) concentration. PGE2 is eliminated from brain across the blood-brain barrier (BBB) in mice, and this process is inhibited by intracerebral or intravenous pre-administration of anti-inflammatory drugs and antibiotics such as cefmetazole and cefazolin that inhibit multidrug resistance-associated protein 4 (Mrp4/Abcc4)-mediated PGE2 transport. The purpose of this study was to examine the effect of LPS-induced inflammation on PGE2 elimination from brain, and whether antibiotics further inhibit PGE2 elimination in LPS-treated mice.

Methods

[3H]PGE2 elimination across the BBB of intraperitoneally LPS-treated mice was assessed by the brain efflux index (BEI) method. Transporter protein amounts in brain capillaries were quantified by liquid chromatography-tandem mass spectrometry.

Results

The apparent elimination rate of [3H]PGE2 from brain was lower by 87%, in LPS-treated mice compared with saline-treated mice. The Mrp4 protein amount was unchanged in brain capillaries of LPS-treated mice compared with saline-treated mice, while the protein amounts of organic anion transporter 3 (Oat3/Slc22a8) and organic anion transporting polypeptide 1a4 (Oatp1a4/Slco1a4) were decreased by 26% and 39%, respectively. Either intracerebral or intravenous pre-administration of cefmetazole further inhibited PGE2 elimination in LPS-treated mice. However, intracerebral or intravenous pre-administration of cefazolin had little effect on PGE2 elimination in LPS-treated mice, or in LPS-untreated mice given Oat3 and Oatp1a4 inhibitors. These results indicate that peripheral administration of cefmetazole inhibits PGE2 elimination across the BBB in LPS-treated mice.

Conclusion

PGE2 elimination across the BBB is attenuated in an LPS-induced mouse model of inflammation. Peripheral administration of cefmetazole further inhibits PGE2 elimination in LPS-treated mice.
Appendix
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Metadata
Title
Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole
Authors
Shin-ichi Akanuma
Yasuo Uchida
Sumio Ohtsuki
Masanori Tachikawa
Tetsuya Terasaki
Ken-ichi Hosoya
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2011
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/2045-8118-8-24

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