PMID- 23251381
OWN - NLM
STAT- MEDLINE
DCOM- 20130603
LR  - 20240318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Volatile anesthetics influence blood-brain barrier integrity by modulation of 
      tight junction protein expression in traumatic brain injury.
PG  - e50752
LID - 10.1371/journal.pone.0050752 [doi]
LID - e50752
AB  - 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.
FAU - Thal, Serge C
AU  - Thal SC
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University, Mainz, Germany. thal@uni-mainz.de
FAU - Luh, Clara
AU  - Luh C
FAU - Schaible, Eva-Verena
AU  - Schaible EV
FAU - Timaru-Kast, Ralph
AU  - Timaru-Kast R
FAU - Hedrich, Jana
AU  - Hedrich J
FAU - Luhmann, Heiko J
AU  - Luhmann HJ
FAU - Engelhard, Kristin
AU  - Engelhard K
FAU - Zehendner, Christoph M
AU  - Zehendner CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121210
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Claudin-5)
RN  - 0 (Methyl Ethers)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 38LVP0K73A (Sevoflurane)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Anesthetics, Inhalation/*pharmacology
MH  - Animals
MH  - Blood-Brain Barrier/*drug effects/metabolism/physiopathology
MH  - Brain Edema/metabolism/physiopathology
MH  - Brain Injuries/*metabolism/physiopathology
MH  - Cell Line
MH  - Claudin-5/metabolism
MH  - Coculture Techniques
MH  - Endothelial Cells/drug effects/metabolism
MH  - Isoflurane/*pharmacology
MH  - Male
MH  - Methyl Ethers/*pharmacology
MH  - Mice
MH  - Sevoflurane
MH  - Tight Junctions/*drug effects/metabolism
MH  - Zonula Occludens-1 Protein/metabolism
PMC - PMC3519465
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/12/20 06:00
MHDA- 2013/06/05 06:00
PMCR- 2012/12/10
CRDT- 2012/12/20 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2012/10/25 00:00 [accepted]
PHST- 2012/12/20 06:00 [entrez]
PHST- 2012/12/20 06:00 [pubmed]
PHST- 2013/06/05 06:00 [medline]
PHST- 2012/12/10 00:00 [pmc-release]
AID - PONE-D-12-18390 [pii]
AID - 10.1371/journal.pone.0050752 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e50752. doi: 10.1371/journal.pone.0050752. Epub 2012 Dec 10.