Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.

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...

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Autores principales:	Serge C Thal, Clara Luh, Eva-Verena Schaible, Ralph Timaru-Kast, Jana Hedrich, Heiko J Luhmann, Kristin Engelhard, Christoph M Zehendner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60377b5fe82744568c1728af48d3ae2c
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spelling	oai:doaj.org-article:60377b5fe82744568c1728af48d3ae2c2021-11-18T08:05:51ZVolatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.1932-620310.1371/journal.pone.0050752https://doaj.org/article/60377b5fe82744568c1728af48d3ae2c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251381/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Disruption 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.Serge C ThalClara LuhEva-Verena SchaibleRalph Timaru-KastJana HedrichHeiko J LuhmannKristin EngelhardChristoph M ZehendnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50752 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Serge C Thal Clara Luh Eva-Verena Schaible Ralph Timaru-Kast Jana Hedrich Heiko J Luhmann Kristin Engelhard Christoph M Zehendner Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
description	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.
format	article
author	Serge C Thal Clara Luh Eva-Verena Schaible Ralph Timaru-Kast Jana Hedrich Heiko J Luhmann Kristin Engelhard Christoph M Zehendner
author_facet	Serge C Thal Clara Luh Eva-Verena Schaible Ralph Timaru-Kast Jana Hedrich Heiko J Luhmann Kristin Engelhard Christoph M Zehendner
author_sort	Serge C Thal
title	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
title_short	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
title_full	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
title_fullStr	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
title_full_unstemmed	Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
title_sort	volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/60377b5fe82744568c1728af48d3ae2c
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Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.

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