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Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult.

David HN, Haelewyn B, Degoulet M, Colomb DG, Risso JJ, Abraini JH - PLoS ONE (2012)

Bottom Line: Contrasting with its beneficial effect at the cortical level, we show that postischemic argon increases MCAO-induced subcortical brain damage and provides no improvement of neurologic outcome as compared to control animals.These results extend previous data on the neuroprotective action of argon.Also, the effects of argon are discussed as regards to the oxygen-like chemical, pharmacological, and physical properties of argon.

View Article: PubMed Central - PubMed

Affiliation: Université Laval, Centre de Recherche - Centre Hospitalier Affilié Universitaire Hôtel-Dieu de Lévis, Lévis, Québec, Canada.

ABSTRACT
In vitro studies have well established the neuroprotective action of the noble gas argon. However, only limited data from in vivo models are available, and particularly whether postexcitotoxic or postischemic argon can provide neuroprotection in vivo still remains to be demonstrated. Here, we investigated the possible neuroprotective effect of postexcitotoxic-postischemic argon both ex vivo in acute brain slices subjected to ischemia in the form of oxygen and glucose deprivation (OGD), and in vivo in rats subjected to an intrastriatal injection of N-methyl-D-aspartate (NMDA) or to the occlusion of middle-cerebral artery (MCAO). We show that postexcitotoxic-postischemic argon reduces OGD-induced cell injury in brain slices, and further reduces NMDA-induced brain damage and MCAO-induced cortical brain damage in rats. Contrasting with its beneficial effect at the cortical level, we show that postischemic argon increases MCAO-induced subcortical brain damage and provides no improvement of neurologic outcome as compared to control animals. These results extend previous data on the neuroprotective action of argon. Particularly, taken together with previous in vivo data that have shown that intraischemic argon has neuroprotective action at both the cortical and subcortical level, our findings on postischemic argon suggest that this noble gas could be administered during but not after ischemia, i.e. before but not after reperfusion has occurred, in order to provide cortical neuroprotection and to avoid increasing subcortical brain damage. Also, the effects of argon are discussed as regards to the oxygen-like chemical, pharmacological, and physical properties of argon.

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Reduction by argon (Ar) of OGD-induced LDH release.(A) Concentration-response effects of argon (Ar) on OGD-induced LDH release (n = 23–27 per group). Exposure to OGD led to an increase in LDH release. Argon of 37.5 vol% to 75 vol% significantly reduced the increase in LDH release induced by OGD. (B) Time-course effects of OGD-induced cell injury and argon-induced neuroprotection. Cell injury induced by OGD as well as neuroprotection by argon increased as a function of time during the 3-h “reperfusion” period. Data are expressed as mean ± SEM. *P<0.05 vs OGD control slices; +P<0.05 vs sham slices.
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pone-0030934-g001: Reduction by argon (Ar) of OGD-induced LDH release.(A) Concentration-response effects of argon (Ar) on OGD-induced LDH release (n = 23–27 per group). Exposure to OGD led to an increase in LDH release. Argon of 37.5 vol% to 75 vol% significantly reduced the increase in LDH release induced by OGD. (B) Time-course effects of OGD-induced cell injury and argon-induced neuroprotection. Cell injury induced by OGD as well as neuroprotection by argon increased as a function of time during the 3-h “reperfusion” period. Data are expressed as mean ± SEM. *P<0.05 vs OGD control slices; +P<0.05 vs sham slices.

Mentions: First, we investigated the effect of postischemic argon on neuronal injury induced by OGD in acute brain slices. Cell injury was assessed by the release of OGD-induced lactate dehydrogenase (LDH). Exposure to OGD led to a sustained increase of LDH release compared to sham slices (P<0.0001; Fig. 1A,B). Argon given after OGD, i.e. during the postischemic “reperfusion” period, led to significant changes in OGD-induced LDH release (P<0.0001), so that LDH levels with argon of 37.5 vol% to 75 vol% were lower than those recorded in OGD control slices exposed to nitrogen (P<0.01−0.0001; Fig. 1A). Maximal neuroprotection occurred with argon at 50 vol%, and increased with time (Fig. 1B).


Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult.

David HN, Haelewyn B, Degoulet M, Colomb DG, Risso JJ, Abraini JH - PLoS ONE (2012)

Reduction by argon (Ar) of OGD-induced LDH release.(A) Concentration-response effects of argon (Ar) on OGD-induced LDH release (n = 23–27 per group). Exposure to OGD led to an increase in LDH release. Argon of 37.5 vol% to 75 vol% significantly reduced the increase in LDH release induced by OGD. (B) Time-course effects of OGD-induced cell injury and argon-induced neuroprotection. Cell injury induced by OGD as well as neuroprotection by argon increased as a function of time during the 3-h “reperfusion” period. Data are expressed as mean ± SEM. *P<0.05 vs OGD control slices; +P<0.05 vs sham slices.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3285153&req=5

pone-0030934-g001: Reduction by argon (Ar) of OGD-induced LDH release.(A) Concentration-response effects of argon (Ar) on OGD-induced LDH release (n = 23–27 per group). Exposure to OGD led to an increase in LDH release. Argon of 37.5 vol% to 75 vol% significantly reduced the increase in LDH release induced by OGD. (B) Time-course effects of OGD-induced cell injury and argon-induced neuroprotection. Cell injury induced by OGD as well as neuroprotection by argon increased as a function of time during the 3-h “reperfusion” period. Data are expressed as mean ± SEM. *P<0.05 vs OGD control slices; +P<0.05 vs sham slices.
Mentions: First, we investigated the effect of postischemic argon on neuronal injury induced by OGD in acute brain slices. Cell injury was assessed by the release of OGD-induced lactate dehydrogenase (LDH). Exposure to OGD led to a sustained increase of LDH release compared to sham slices (P<0.0001; Fig. 1A,B). Argon given after OGD, i.e. during the postischemic “reperfusion” period, led to significant changes in OGD-induced LDH release (P<0.0001), so that LDH levels with argon of 37.5 vol% to 75 vol% were lower than those recorded in OGD control slices exposed to nitrogen (P<0.01−0.0001; Fig. 1A). Maximal neuroprotection occurred with argon at 50 vol%, and increased with time (Fig. 1B).

Bottom Line: Contrasting with its beneficial effect at the cortical level, we show that postischemic argon increases MCAO-induced subcortical brain damage and provides no improvement of neurologic outcome as compared to control animals.These results extend previous data on the neuroprotective action of argon.Also, the effects of argon are discussed as regards to the oxygen-like chemical, pharmacological, and physical properties of argon.

View Article: PubMed Central - PubMed

Affiliation: Université Laval, Centre de Recherche - Centre Hospitalier Affilié Universitaire Hôtel-Dieu de Lévis, Lévis, Québec, Canada.

ABSTRACT
In vitro studies have well established the neuroprotective action of the noble gas argon. However, only limited data from in vivo models are available, and particularly whether postexcitotoxic or postischemic argon can provide neuroprotection in vivo still remains to be demonstrated. Here, we investigated the possible neuroprotective effect of postexcitotoxic-postischemic argon both ex vivo in acute brain slices subjected to ischemia in the form of oxygen and glucose deprivation (OGD), and in vivo in rats subjected to an intrastriatal injection of N-methyl-D-aspartate (NMDA) or to the occlusion of middle-cerebral artery (MCAO). We show that postexcitotoxic-postischemic argon reduces OGD-induced cell injury in brain slices, and further reduces NMDA-induced brain damage and MCAO-induced cortical brain damage in rats. Contrasting with its beneficial effect at the cortical level, we show that postischemic argon increases MCAO-induced subcortical brain damage and provides no improvement of neurologic outcome as compared to control animals. These results extend previous data on the neuroprotective action of argon. Particularly, taken together with previous in vivo data that have shown that intraischemic argon has neuroprotective action at both the cortical and subcortical level, our findings on postischemic argon suggest that this noble gas could be administered during but not after ischemia, i.e. before but not after reperfusion has occurred, in order to provide cortical neuroprotection and to avoid increasing subcortical brain damage. Also, the effects of argon are discussed as regards to the oxygen-like chemical, pharmacological, and physical properties of argon.

Show MeSH
Related in: MedlinePlus