Neuroprotection against traumatic brain injury by xenon but not argon, is mediated by inhibition at the NMDA receptor glycine site
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Background. The inert anesthetic gas xenon is neuroprotective in models of brain injury. We
investigate the neuroprotective mechanisms of the inert gases xenon, argon, krypton, neon and
helium in an in vitro model of traumatic brain injury.
Methods. We use an in vitro model using mouse organotypic hippocampal brain-slices, subjected
to a focal mechanical trauma, with injury quantified by propidium-iodide fluorescence. Patch-clamp
electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate
(NMDA)-receptors and TREK-1 channels, two molecular targets likely to play a role in
neuroprotection.
Results. Xenon(50%) and, to a lesser extent, argon(50%) are neuroprotective against traumatic
injury when applied following injury [xenon 43±1% protection 72hours after injury (N=104); argon
30±6% protection (N=44); mean±SEM]. Helium, neon and krypton are devoid of neuroprotective
effect. Xenon(50%) prevents development of secondary injury up to 48 hours after trauma.
Argon(50%) attenuates secondary injury, but is less effective than xenon [xenon 50±5% reduction
in secondary injury 72hours after injury (N=104); argon 34±8% reduction (N=44); mean±SEM].
Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive
inhibition at the NMDA receptor glycine-site mediating xenon neuroprotection against traumatic
brain injury. Xenon inhibits NMDA receptors and activates TREK-1 channels, while argon,
krypton, neon and helium have no effect on these ion-channels.
Conclusions. Xenon neuroprotection against traumatic brain injury can be reversed by elevating
the glycine concentration, consistent with inhibition at the NMDA-receptor glycine site playing a
significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
investigate the neuroprotective mechanisms of the inert gases xenon, argon, krypton, neon and
helium in an in vitro model of traumatic brain injury.
Methods. We use an in vitro model using mouse organotypic hippocampal brain-slices, subjected
to a focal mechanical trauma, with injury quantified by propidium-iodide fluorescence. Patch-clamp
electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate
(NMDA)-receptors and TREK-1 channels, two molecular targets likely to play a role in
neuroprotection.
Results. Xenon(50%) and, to a lesser extent, argon(50%) are neuroprotective against traumatic
injury when applied following injury [xenon 43±1% protection 72hours after injury (N=104); argon
30±6% protection (N=44); mean±SEM]. Helium, neon and krypton are devoid of neuroprotective
effect. Xenon(50%) prevents development of secondary injury up to 48 hours after trauma.
Argon(50%) attenuates secondary injury, but is less effective than xenon [xenon 50±5% reduction
in secondary injury 72hours after injury (N=104); argon 34±8% reduction (N=44); mean±SEM].
Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive
inhibition at the NMDA receptor glycine-site mediating xenon neuroprotection against traumatic
brain injury. Xenon inhibits NMDA receptors and activates TREK-1 channels, while argon,
krypton, neon and helium have no effect on these ion-channels.
Conclusions. Xenon neuroprotection against traumatic brain injury can be reversed by elevating
the glycine concentration, consistent with inhibition at the NMDA-receptor glycine site playing a
significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
Editor(s)
Eisenach, JC
Date Issued
2013-11-01
Date Acceptance
2013-11-01
Citation
Anesthesiology, 2013, 119 (5), pp.1137-1148
ISSN
1528-1175
Publisher
Lippincott, Williams &; Wilkins
Start Page
1137
End Page
1148
Journal / Book Title
Anesthesiology
Volume
119
Issue
5
Copyright Statement
This is not the final version of record, which can be found at https://dx.doi.org/10.1097/ALN.0b013e3182a2a265.
Identifier
PII: PMID: 23867231
Publication Status
Published