[In vitro effects of anaesthetic agents on the blood-brain barrier].
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-gamma-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.


CONCLUSIONS
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.
Fischer
S
S
Abteilung für Anästhesiologie und Intensivmedizin, Kerckhoff-Klinik GmbH, Bad Nauheim. s.fischer@kerckhoff.mpg.de
Renz
D
D
Kleinstück
J
J
Schaper
W
W
Karliczek
G F
GF
D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015152:Blotting, Northern; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000777:Anesthetics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D042461:Vascular Endothelial Growth Factor A