Marc Lemaire

Publications (8)40.83 Total impact

• Article: Neuroprotection by nitrous oxide: facts and evidence.

  Benoit Haelewyn, Hélène N David, Christophe Rouillon, Laurent Chazalviel, Myriam Lecocq, Jean-Jacques Risso, Marc Lemaire, Jacques H Abraini
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  ABSTRACT: Preliminary studies have shown that nitrous oxide, like xenon, may possess potentially neuroprotective properties. However, because of its possible neurotoxic and proneurotoxic effects (obtained under particular conditions) and its bad reputation at anesthetic concentrations, no thorough investigations have been performed on the potentially neuroprotective properties of nitrous oxide. The aim of this study was to investigate the possible neuroprotective effects of nitrous oxide at nonanesthetic concentrations on different models of excitotoxic insult and brain ischemia. Here, we show using multiple models of ex vivo and in vivo excitotoxic insults and brain ischemia that nitrous oxide, administered alone at nonanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia to reduction of subsequent cell injury. In vivo, in rats subjected to transient cerebral ischemia, nitrous oxide at 50 vol% offers full neuroprotection at both the histologic and neurologic outcome levels when administered up to 2 hrs, but not 3 hrs, after ischemia onset. These data provide experimental evidence that nitrous oxide, which is a cost-efficient and easily available gas, has potentially neuroprotective properties in rodents when given alone at nonanesthetic concentrations. Therefore, because there is a lot at stake for the affected patients and society--in terms of easy access to treatment, profound impact of brain damage, cost of treatment, and subsequent financial cost on society--we believe that further studies should investigate thoroughly the possible potential clinical interest of nitrous oxide for the treatment of ischemic stroke in terms of optimal indications, type of ischemic injury, duration and time points for treatment, and the optimal concentration of gas to be used in clinical circumstances.
  Critical care medicine 10/2008; 36(9):2651-9. · 6.37 Impact Factor
• Article: Neuroprotective effects of xenon: a therapeutic window of opportunity in rats subjected to transient cerebral ischemia.

  Hélène N David, Benoit Haelewyn, Christophe Rouillon, Myriam Lecoq, Laurent Chazalviel, Gabriela Apiou, Jean-Jacques Risso, Marc Lemaire, Jacques H Abraini
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  ABSTRACT: 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.
  The FASEB Journal 05/2008; 22(4):1275-86. · 5.71 Impact Factor
• Article: Protein crystallography under xenon and nitrous oxide pressure: comparison with in vivo pharmacology studies and implications for the mechanism of inhaled anesthetic action.

  Nathalie Colloc'h, Jana Sopkova-de Oliveira Santos, Pascal Retailleau, Denis Vivarès, Françoise Bonneté, Béatrice Langlois d'Estainto, Bernard Gallois, Alain Brisson, Jean-Jacques Risso, Marc Lemaire, Thierry Prangé, Jacques H Abraini
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  ABSTRACT: In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe) and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate (NMDA) receptor. Using x-ray crystallography, we examined the binding characteristics of these two gases on two soluble proteins as structural models: urate oxidase, which is a prototype of a variety of intracellular globular proteins, and annexin V, which has structural and functional characteristics that allow it to be considered as a prototype for the NMDA receptor. The structure of these proteins complexed with Xe and N(2)O were determined. One N(2)O molecule or one Xe atom binds to the same main site in both proteins. A second subsite is observed for N(2)O in each case. The gas-binding sites are always hydrophobic flexible cavities buried within the monomer. Comparison of the effects of Xe and N(2)O on urate oxidase and annexin V reveals an interesting relationship with the in vivo pharmacological effects of these gases, the ratio of the gas-binding sites' volume expansion and the ratio of the narcotic potency being similar. Given these data, we propose that alterations of cytosolic globular protein functions by general anesthetics would be responsible for the early stages of anesthesia such as amnesia and hypnosis and that additional alterations of ion-channel membrane receptor functions are required for deeper effects that progress to "surgical" anesthesia.
  Biophysical Journal 02/2007; 92(1):217-24. · 3.65 Impact Factor
• Article: Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization.

  Hélène N David, Marc Ansseau, Marc Lemaire, Jacques H Abraini
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  ABSTRACT: Amphetamine administration induces stimulation-independent dopamine release in the nucleus accumbens (NAcc) through reverse dopamine transport, a critical neurochemical event involved in its psychostimulant action, and furthermore decreases stimulation-dependent vesicular dopamine release. These effects may involve possible indirect glutamatergic mechanisms. We investigated the effects of nitrous oxide and xenon, which possess antagonistic action at the N-methyl-D-aspartate (NMDA) receptor, on brain slices ex vivo on amphetamine-induced changes in carrier-mediated and KCl-evoked dopamine release in the NAcc, and in vivo on amphetamine-induced locomotor sensitization. Like the low-affinity NMDA receptor antagonist memantine, but not the prototypical compound MK-801, nitrous oxide and xenon at appropriate concentrations blocked both the increase in carrier-mediated dopamine release and locomotor sensitization produced by amphetamine. In contrast to what has generally been found using prototypical NMDA receptor antagonists, these data regarding the effect of memantine, nitrous oxide, and xenon support the hypothesis that activation of certain NMDA receptors (possibly those containing the NR1a/NR2D subunit) in the NAcc is involved in the amphetamine-induced increase in carrier-mediated dopamine release and the development of behavioral sensitization to amphetamine. Nitrous oxide, xenon, and memantine may be of therapeutic interest for treating drug dependence.
  Biological Psychiatry 08/2006; 60(1):49-57. · 8.28 Impact Factor
• Article: Postischemic nitrous oxide alone versus intraischemic nitrous oxide in the presence of isoflurane: what it may change for neuroprotection against cerebral stroke in the rat.

  Jacques H Abraini, Hélène N David, Eric T MacKenzie, Marc Lemaire
  Anesthesia & Analgesia 09/2005; 101(2):614; author reply 614. · 3.29 Impact Factor
• Article: Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon.

  Jacques H Abraini, Hélène N David, Marc Lemaire
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  ABSTRACT: Despite the beneficial effects of prototypical glutamatergic receptor antagonists in animal models, the pharmacological attempts by the use of such agents have met with very limited clinical success because these compounds produce adverse side effects and possess an intrinsic neurotoxicity at neuroprotective and therapeutic concentrations. Interestingly, nitrous oxide and xenon, which are anesthetic gases with a remarkably safe clinical profile, have been shown to be effective inhibitors of the NMDA receptor. We briefly review accumulating evidence that nitrous oxide and xenon at subanesthetic concentrations may have potentially neuroprotective and therapeutic properties, with a particular focus on their beneficial effects on ischemia-induced neuronal death and amphetamine-induced sensitization. Nitrous oxide at 75-vol% and xenon up to 70-vol% reduce ischemia-induced neuronal death induced by occlusion of the middle cerebral artery in rodents, and decrease NMDA-induced Ca2+ influx in neuronal cell cultures, a critical event involved in excitotoxicity. Nitrous oxide at 75-vol% and xenon at 50-vol% further reduced amphetamine-induced locomotor sensitization in rodents. However, at a higher concentration of 75-vol%, xenon shows potentially neurotoxic properties and adverse side effects. Because both agents are rapidly eliminated from the body, it is plausible that their administration at appropriate subanesthetic neuroprotective and therapeutic concentrations may not be associated, in contrast with prototypical NMDA receptor antagonists, with adverse side effects and potentially neurotoxicity. Finally, the possible therapeutic implications in humans are discussed.
  Annals of the New York Academy of Sciences 09/2005; 1053:289-300. · 3.15 Impact Factor
• Article: Neuroprotection by nitrous oxide and xenon and its relation to minimum alveolar concentration.

  Jacques H Abraini, Hélène N David, Olivier Nicole, Eric T MacKenzie, Alain Buisson, Marc Lemaire
  Anesthesiology 08/2004; 101(1):260-1; author reply 261. · 5.36 Impact Factor
• Article: Reduction of ischemic brain damage by nitrous oxide and xenon.

  Helene N David, Frederic Leveille, Laurent Chazalviel, Eric T MacKenzie, Alain Buisson, Marc Lemaire, Jacques H Abraini
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  ABSTRACT: Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death. The authors have shown that both nitrous oxide at 75 vol% and xenon at 50 vol% reduce ischemic neuronal death in the cortex by 70% and further decrease NMDA-induced Ca2+ influx by 30%. In addition, xenon at 50%, but not nitrous oxide at 75 vol%, further decreases ischemic brain damage in the striatum (a subcortical structure that is known to be resistant to neuroprotective interventions). However, at a higher concentration (75 vol%), xenon exhibits potentially neurotoxic effects. The mechanisms of the neuroprotective and potentially neurotoxic effects of nitrous oxide and xenon, as well as the possible therapeutic implications in humans, are discussed.
  Journal of Cerebral Blood Flow &#38 Metabolism 11/2003; 23(10):1168-73. · 5.01 Impact Factor