Autoren:	Thal, Serge Luh, Clara Schaible, Eva-Verena Timaru-Kast, Ralph Hedrich, Jana Luhmann, Heiko Engelhard, Kristin Zehendner, Christoph M.
Titel:	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury
Online-Publikationsdatum:	31-Jan-2013
Erscheinungsdatum:	2012
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-741
URN:	urn:nbn:de:hebis:77-33080
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/3.0/
Zeitschrift:	PLoS one 7 12
Seitenzahl oder Artikelnummer:	e50752
Verlag:	PLoS
Verlagsort:	Lawrence, Kan.
Erscheinungsdatum:	2012
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0050752
DOI der Originalveröffentlichung:	10.1371/journal.pone.0050752
Enthalten in den Sammlungen:	JGU-Publikationen