Evidence map›Paper›PMID 21199574›Full record

ArticleBMC medical imaging2011

(R)-[11C]verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus.

Stina Syvänen, Gert Luurtsema, Carla F M Molthoff, Albert D Windhorst, Marc C Huisman, Adriaan A Lammertsma, Rob A Voskuyl, Elizabeth C de Lange

Abstract read
In one paragraph

Article in BMC medical imaging, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Nonlinear Mixed-Effects Models for PET Data.IEEE transactions on bio-medical engineering · 2019
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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

8 authors.

Stina SyvänenDivision of Pharmacology, LACDR, Leiden University, P,O, Box 9502, 2300 RA Leiden, The Netherlands. s.syvanen@lacdr.leidenuniv.nl
Gert Luurtsema
Carla F M Molthoff
Albert D Windhorst
Marc C Huisman
Adriaan A Lammertsma
Rob A Voskuyl
Elizabeth C de Lange

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIncreased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate.

methods(R)-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM).

resultsAll data analysis approaches indicated only modest differences in brain distribution of (R)-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats.

conclusionsP-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

Indexed as

Kainic AcidAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Blood-Brain BarrierCalcium Channel BlockersCarbon RadioisotopesMalePositron-Emission TomographyRadiopharmaceuticalsRatsRats, Sprague-DawleyStatus EpilepticusTissue DistributionVerapamilATP Binding Cassette Transporter, Subfamily B, Member 1Calcium Channel BlockersCarbon RadioisotopesKainic AcidRadiopharmaceuticalsVerapamil

Identifiers

PMID21199574
PMCPMC3022839

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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.