ASD participated in subject recruitment, microvascular analysis, and data analysis. GAS participated since in manuscript preparation and editing. AA participated in data analysis and manuscript preparation.AcknowledgementsThis work was supported by the American Heart Association (0660058Z–KCD) and National Institutes of Health (K23HL071246–KCD, K08DK073519–AA, and RR-59).
Every noble work is at first impossible.Thomas CarlyleThe quest for a therapeutic to ameliorate ischemic and traumatic brain injury is certainly a noble ideal, but, thus far, a futile endeavor. In the previous issue of Critical Care, Loetscher and colleagues [1] provided further evidence that the inert, noble gases may have ameliorative properties in the setting of acute neuronal injury.

Stimulated by a shared interest in the neuroprotective properties of another noble gas, xenon [2-4], they have shifted their focus to argon, a gas that is more abundant and cheaper to obtain. In their current investigation, they demonstrate that argon is neuroprotective when applied after an oxygen-glucose deprivation (OGD) or traumatic injury in organotypic hippocampal slice cultures in vitro. The models the authors employ are robust; the cultured slices have intact synaptic networks, replicating the in vivo setting well; OGD is a well-described simulation of ischemic brain injury [3]; similarly, the trauma model replicates the clinical situation [2]. Loetscher and colleagues report a dose-responsive neuroprotective effect, with 50% argon appearing to be the optimal concentration for neuroprotection.

Furthermore, argon was even neuroprotective when administered 3 hours after the injury. Although this report used only in vitro models, it is a foundation on which to base further studies that may further reveal argon’s potential in a field largely bereft of interventions to improve neurological outcome from ischemic or traumatic brain injury.We recently reported that argon (75%) prevented neuronal injury from OGD in vitro but that the protection afforded was inferior to that of xenon [3]. Xenon has been shown to be neuroprotective in multiple GSK-3 models and species and has now entered clinical trials for neonatal hypoxic-ischemic brain injury (TOBYXe; NCT00934700) [4,5]. If argon is also to be exploited clinically, it too must undergo rigorous examination in different animal models, species, laboratories, and clinically relevant injury settings [6]. While at this stage argon fulfills some criteria, it would be imprudent, in the absence of in vivo data, to hail argon as the elusive neuroprotective agent.