Evidence map›Paper›PMID 34959403›Full record

ArticlePharmaceutics2021

An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.

Risa Sato, Kotaro Ohmori, Mina Umetsu, Masaki Takao, Mitsutoshi Tano, Gerald Grant, Brenda Porter, Anthony Bet, Tetsuya Terasaki, Yasuo Uchida

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

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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

10 authors at 3 institutions in 2 countries.

Risa SatoGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Kotaro OhmoriGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Mina UmetsuGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Masaki TakaoDepartment of Neurology and Brain Bank, Mihara Memorial Hospital, Isesaki 372-0006, Japan.
Mitsutoshi TanoDepartment of Neurology and Brain Bank, Mihara Memorial Hospital, Isesaki 372-0006, Japan.
Gerald GrantDepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-2651-4603
Brenda PorterDepartment of Neurology, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-6346-7327
Anthony BetDepartment of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
Tetsuya TerasakiGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.ORCID 0000-0002-6332-7575
Yasuo UchidaGraduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.ORCID 0000-0001-9860-1979
Tohoku University · JPStanford University · USInstitute of Brain and Blood Vessels · JP

Funding

Japan Society for the Promotion of Science KAKENHI: 18KK0446Japan Society for the Promotion of Science KAKENHI: 20H03399Ministry of Education, Culture, Sports, Science and Technology KAKENHI: 20H04690Ministry of Education, Culture, Sports, Science and Technology KAKENHI: 20H05495Takeda Science Foundation no grant number
6 · The paper itself

Abstract

The purpose of the present study was to quantitatively elucidate the levels of protein expression of anti-epileptic-drug (AED) transporters, metabolizing enzymes and tight junction molecules at the blood-brain barrier (BBB) in the focal site of epilepsy patients using accurate SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Brain capillaries were isolated from focal sites in six epilepsy patients and five normal brains; tryptic digests were produced and subjected to SWATH analysis. MDR1 and BCRP were significantly downregulated in the epilepsy group compared to the normal group. Out of 16 AED-metabolizing enzymes detected, the protein expression levels of GSTP1, GSTO1, CYP2E1, ALDH1A1, ALDH6A1, ALDH7A1, ALDH9A1 and ADH5 were significantly 2.13-, 6.23-, 2.16-, 2.80-, 1.73-, 1.67-, 2.47- and 2.23-fold greater in the brain capillaries of epileptic patients than those of normal brains, respectively. The protein expression levels of Claudin-5, ZO-1, Catenin alpha-1, beta-1 and delta-1 were significantly lower, 1.97-, 2.51-, 2.44-, 1.90- and 1.63-fold, in the brain capillaries of epileptic patients compared to those of normal brains, respectively. Consistent with these observations, leakage of blood proteins was also observed. These results provide for a better understanding of the therapeutic effect of AEDs and molecular mechanisms of AED resistance in epileptic patients.

Indexed as

anti-epileptic drugblood–brain barrierenzymeepilepsySWATHtight junctiontransporter

Identifiers

PMID34959403
PMCPMC8708024
OpenAlexW4200393238

What OpenQuestion holds

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LicenceCC BY
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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.