Evidence map›Paper›PMID 26091107›Full record

ArticlePloS one2015

In Vitro Induction of Endothelial Apoptosis of the Post-Hypoxic Blood-Brain Barrier by Isoflurane but Not by Sevoflurane and Midazolam.

Michael S Dittmar, Walter Petermichl, Regina Lindner, Barbara Sinner, Bernhard M Graf, Felix Schlachetzki, Michael Gruber

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Physiological and Pathological Remodeling of Cerebral Microvessels.International journal of molecular sciences · 2022
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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

7 authors at 2 institutions in 1 country.

Michael S DittmarDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
Walter PetermichlDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
Regina LindnerDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
Barbara SinnerDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
Bernhard M GrafDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
Felix SchlachetzkiDepartment of Neurology, Bezirksklinikum Regensburg, University of Regensburg, Regensburg, Germany.
Michael GruberDepartment of Anesthesiology, Regensburg University Medical Center, Regensburg, Germany.
University Hospital Regensburg · DEUniversity of Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe effects of anesthetics on the injured brain continue to be the subject of controversial discussion. Since isoflurane has recently been shown to induce apoptosis of cerebral endothelial cells, this study compared different anesthetic compounds regarding their potential to induce cerebro-vascular apoptosis.

methodsThe in vitro model of the blood-brain barrier used in this study consisted of astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVEC) has been used. After 24 h of deep hypoxia and reoxygenation or control treatment, AC-HUVEC were exposed to 0, 0.5, 1.0, or 2.0 times the minimum alveolar concentration of isoflurane or sevoflurane, or 0, 75, 150, or 300 nM of midazolam for 2 h. After 24 h, AC-HUVEC were harvested, and the degree of apoptosis was assessed by means of Western blots for the Bax and Bcl-2 ratio and, for controls and the highest concentration groups, terminal deoxynucleotidyl-mediated dUTP-biotin nick end labeling (TUNEL).

resultsWithout hypoxic pretreatment, 2.0 MAC of isoflurane slightly increased TUNEL intensity compared to control and sevoflurane, but without any significant changes in the Bax and Bcl-2 ratio. After hypoxic pretreatment, exposure to isoflurane led to a multifold increase in the Bax and Bcl-2 ratio in a dose dependent manner, which was also significantly higher than the ratio observed in the 2 MAC sevoflurane group. TUNEL intensity in the post-hypoxic 2 MAC isoflurane group was increased by a factor of 11 vs. control and by 40 vs. sevoflurane. Sevoflurane and midazolam did not significantly alter these markers of apoptosis, when compared to the control group.

conclusionsIsoflurane administered after hypoxia elevates markers of apoptosis in endothelial cells transdifferentiated to the cerebro-vascular endothelium. Endothelial apoptosis may be a previously underestimated mechanism of anesthetic neurotoxicity. Administration of high concentrations of isoflurane in experimental settings may have negative effects on the blood-brain barrier.

Indexed as

Apoptosisbcl-2-Associated X ProteinBlood-Brain BarrierCell HypoxiaHumansHuman Umbilical Vein Endothelial CellsIsofluraneMethyl EthersMidazolamProto-Oncogene Proteins c-bcl-2Sevofluranebcl-2-Associated X ProteinIsofluraneMethyl EthersMidazolamProto-Oncogene Proteins c-bcl-2Sevoflurane

Identifiers

PMID26091107
PMCPMC4475016
OpenAlexW1857468444

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.