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In-vitro-Effekte von Anästhetika auf die Blut-Hirn-Schranke

In vitro effects of anaesthetic agents on the blood-brain barrier

Der Anaesthesist volume 53, pages 1177–1184 (2004)Cite this article

Zusammenfassung

Hintergrund

Die Blut-Hirn-Schranke (BHS) bildet eine Schranke zwischen dem Blutkreislauf und dem Gehirn und reguliert die Passage vieler Moleküle. Pathologische Bedingungen, wie Ischämie, führen zu einem Zusammenbruch der BHS. „Vascular endothelial growth factor“ (VEGF) wurde als das Protein identifiziert, dass sowohl in vivo als auch in vitro die Hypoxie-induzierte Hyperpermeabilität der BHS induziert. Zur Eliminierung von Faktoren, die in vivo die Permeabilität der BHS beeinflussen, wurde ein In-vitro-Modell der BHS verwendet, um die Wirkung intravenöser und volatiler Anästhetika auf die Permeabilität und VEGF-Expression unter normoxischen und hypoxischen Bedingungen zu untersuchen.

Methoden

Das In-vitro-Modell der BHS bestand aus primären Kulturen mikrovaskulärer Schweinegehirnendothelzellen (BMEC). Die Permeabilität wurde über die parazelluläre Passage von [3H]Inulin durch den BMEC-Monolayer und die Expression des VEGF mit Northern-blot-Analysen bestimmt.

Ergebnisse

Alle verwendeten intravenösen und volatilen Anästhetika (Etomidat, Ketamin, Fentanyl, Propofol, Midazolam, Natrium-γ-Hydroxybuttersäure sowie Halothan, Enfluran, Isofluran, Sevofluran, Desfluran) veränderten die Permeabilität der In-vitro-BHS und die VEGF-Expression nicht. Hypoxie (2 Vol.-%) steigerte die Permeabilität und die VEGF-Expression deutlich; dies wurde in Gegenwart der Anästhetika nicht verändert.

Schlussfolgerung

Die In-vitro-BHS stellt ein geeignetes Modell dar, um direkte Wirkungen von Anästhetika auf Eigenschaften der BHS, unabhängig von hämodynamischen Parametern, zu untersuchen.

Abstract

Background

The blood-brain barrier (BBB) forms a selective barrier between blood and brain and regulates the passage of most molecules. Pathological conditions such as ischemia lead to breakdown of the BBB. Vascular endothelial growth factor (VEGF) has been shown to be responsible for hypoxia-induced hyperpermeability of the BBB in vivo as well as in vitro. To eliminate factors which alter the permeability of the BBB in vivo, an in vitro model was used to test the effects of intravenous and volatile anesthetics on the permeability and on VEGF expression during normoxia and hypoxia.

Methods

The in vitro model of the BBB consisted of primary cultures of porcine brain microvascular endothelial cells (BMEC). The permeability was measured by the paracellular passage of [3H]inulin across the BMEC monolayer and the expression of VEGF was determined by northern blot analysis.

Results

All intravenous and volatile anesthetics tested (etomidate, ketamine, fentanyl, propofol, midazolam, sodium-γ-hydroxybutyrate as well as halothane, enflurane, isoflurane, sevoflurane, desflurane) did not alter the permeability of the BBB or the expression of VEGF in vitro. Hypoxia (2 vol%) increased the permeability and the VEGF expression significantly which was not altered in the presence of the anesthetics.

Conclusion

The in vitro model represents a suitable model of the BBB to investigate direct effects of anesthetics on functions of the BBB independent of hemodynamic factors.

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Affiliations

  1. Abteilung für Anästhesiologie und Intensivmedizin, Kerckhoff-Klinik GmbH, Bad Nauheim

    S. Fischer, D. Renz & G. F. Karliczek

  2. Abteilung für Experimentelle Kardiologie, Max-Planck Institut für Physiologische and Klinische Forschung, Bad Nauheim

    J. Kleinstück & W. Schaper

  3. Abteilung für Anästhesiologie und Intensivmedizin, Kerckhoff-Klinik GmbH, Benekestr. 2–8, 61231, Bad Nauheim

    S. Fischer

Authors
  1. S. Fischer
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  2. D. Renz
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  3. J. Kleinstück
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  4. W. Schaper
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  5. G. F. Karliczek
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Correspondence to S. Fischer.

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Fischer, S., Renz, D., Kleinstück, J. et al. In-vitro-Effekte von Anästhetika auf die Blut-Hirn-Schranke. Anaesthesist 53, 1177–1184 (2004). https://doi.org/10.1007/s00101-004-0740-y

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Schlüsselwörter

  • Blut-Hirn-Schranke
  • In-vitro-Modell
  • Vascular endothelial growth factor
  • Permeabilität
  • Anästhetika

Keywords

  • Blood-brain barrier
  • In vitro model
  • Vascular endothelial growth factor
  • Permeability
  • Anaesthetics