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.