Neuroprotective effects of xenon: a therapeutic window of opportunity in rats subjected to transient cerebral ischemia

Brain insults are a major cause of acute mortality and chronic morbidity. Given the largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. A series of previous investigations has shown that the noble and anesthetic gas xe...

Full description

Saved in:

Bibliographic Details
Published in:	The FASEB journal Vol. 22; no. 4; pp. 1275 - 1286
Main Authors:	David, Hélène N, Haelewyn, Benoit, Rouillon, Christophe, Lecoq, Myriam, Chazalviel, Laurent, Apiou, Gabriela, Risso, Jean-Jacques, Lemaire, Marc, Abraini, Jacques H
Format:	Journal Article
Language:	English
Published:	United States The Federation of American Societies for Experimental Biology 01-04-2008 Federation of American Societies for Experimental Biology
Subjects:	Animals Dopamine - metabolism dopamine release Ischemic Attack, Transient - drug therapy lactate dehydrogenase Male N-Methylaspartate - pharmacology neurological outcome Neuroprotective Agents - therapeutic use N‐methyl‐D‐aspartate neurotoxicity oxygen‐glucose deprivation Rats Rats, Sprague-Dawley Xenon - therapeutic use
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Brain insults are a major cause of acute mortality and chronic morbidity. Given the largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. A series of previous investigations has shown that the noble and anesthetic gas xenon, which has low-affinity antagonistic properties at the N-methyl-D-aspartate (NMDA) receptor, also exhibits potentially neuroprotective properties with no proven adverse side effects. Surprisingly and in contrast with most drugs that are being developed as therapeutic agents, the dose-response neuroprotective effect of xenon has been poorly studied, although this effect could be of major critical importance for its clinical development as a neuroprotectant. Here we show, using ex vivo and in vivo models of excitotoxic insults and transient brain ischemia, that xenon, administered at subanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia, a critical event known to be involved in excitotoxicity, to reduction of subsequent cell injury and neuronal death. Maximal neuroprotection was obtained with xenon at 50 vol%, a concentration at which xenon further exhibited significant neuroprotective effects in vivo even when administered up to 4 h after intrastriatal NMDA injection and up to at least 2 h after induction of transient brain ischemia.--David, H. N., Haelewyn, B., Rouillon, C., Lecoq, M., Chazalviel, L., Apiou, G., Risso, J.-J., Lemaire, M., Abraini, J. H. Neuroprotective effects of xenon: a therapeutic window of opportunity in rats subjected to transient cerebral ischemia.
Bibliography:	These authors contributed equally to this work. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0892-6638 1530-6860
DOI:	10.1096/fj.07-9420com