Evidence map›Paper›PMID 22014165›Full record

ArticleFluids and barriers of the CNS2011

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

Shin-Ichi Akanuma, Yasuo Uchida, Sumio Ohtsuki, Masanori Tachikawa, Tetsuya Terasaki, Ken-Ichi Hosoya

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 37 citations in OpenAlex.

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  9. Article
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  12. Prostaglandin Transporter OATP2A1/The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  13. Review
  14. Article
  15. Drug transporters in the central nervous system.Clinical pharmacokinetics · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Shin-Ichi AkanumaDivision of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan. terasaki.tetsuya@m.tohoku.ac.jp.
Yasuo Uchida
Sumio Ohtsuki
Masanori Tachikawa
Tetsuya Terasaki
Ken-Ichi Hosoya
Tohoku University · JPUniversity of Toyama · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPeripheral 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.

resultsThe 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.

conclusionPGE2 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.

Identifiers

PMID22014165
PMCPMC3224590
OpenAlexW2106800810

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.