Abstract | BACKGROUND: METHODS: The authors 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 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 after injury ( xenon 43±1% protection at 72 h 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 h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon ( xenon 50±5% reduction in secondary injury at 72 h 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 N-methyl-D-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels. CONCLUSIONS:
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Authors | Katie Harris, Scott P Armstrong, Rita Campos-Pires, Louise Kiru, Nicholas P Franks, Robert Dickinson |
Journal | Anesthesiology
(Anesthesiology)
Vol. 119
Issue 5
Pg. 1137-48
(Nov 2013)
ISSN: 1528-1175 [Electronic] United States |
PMID | 23867231
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anesthetics, Inhalation
- Neuroprotective Agents
- Potassium Channels, Tandem Pore Domain
- Receptors, N-Methyl-D-Aspartate
- potassium channel protein TREK-1
- Xenon
- Argon
- Glycine
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Topics |
- Air Pressure
- Anesthetics, Inhalation
(pharmacology)
- Animals
- Argon
(pharmacology)
- Atmosphere Exposure Chambers
- Brain Injuries
(drug therapy, pathology)
- CA1 Region, Hippocampal
(injuries, pathology)
- Cell Count
- Cell Line
- Electrophysiological Phenomena
- Glycine
(drug effects, pharmacology)
- Hippocampus
(drug effects)
- Humans
- Mice
- Mice, Inbred C57BL
- Neuroprotective Agents
- Organ Culture Techniques
- Potassium Channels, Tandem Pore Domain
(drug effects)
- Rats
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors)
- Xenon
(pharmacology)
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