• Juan He, Ke Xue, Jiayi Liu, Jin-Hua Gu, Bin Peng, Lihua Xu, Guohua Wang, Zhenglin Jiang, Xia Li, and Yunfeng Zhang.
• Stroke Center and Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226019, Jiangsu, China.
• Neurocrit Care. 2022 Aug 1; 37 (1): 9110191-101.

BackgroundInhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke and has exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration, and time point of iAr for acute ischemic stroke are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion injury.MethodsAdult ICR (Institute of Cancer Research) mice were randomly subjected to sham, moderate (1.5 h), or severe (3 h) transient middle cerebral artery occlusion (tMCAO). One hour after tMCAO, the mice were randomized to variable iAr protocols or air. General and focal deficit scores were assessed during double-blind treatment. Infarct volume, overall recovery, and brain edema were analyzed 24 h after cerebral ischemic/reperfusion injury.ResultsCompared with those in the tMCAO-only group, lesion volume (p < 0.0001) and neurologic outcome (general, p < 0.0001; focal, p < 0.0001) were significantly improved in the group administered iAr 1 h after stroke onset (during ischemia). Short-term argon treatment (1 or 3 h) significantly improved the infarct volume (1 vs. 24 h, p < 0.0001; 3 vs. 24 h, p < 0.0001) compared with argon inhalation for 24 h. The concentration of iAr was confirmed to be a key factor in improving focal neurological outcomes relative to that in the tMCAO group, with higher concentrations of iAr showing better effects. Additionally, even though ischemia research has shown an increase in cerebral damage proportional to the ischemia time, argon administration showed significant neuroprotective effects on infarct volume (p < 0.0001), neurological deficits (general, p < 0.0001; focal, p < 0.0001), weight recovery (p < 0.0001), and edema (p < 0.0001) in general, particularly in moderate stroke.ConclusionsTimely iAr administration during ischemia showed optimal neurological outcomes and minimal infarct volumes. Moreover, an appropriate duration of argon administration was important for better neuroprotective efficacy. These findings may provide vital guidance for using argon as a neuroprotective agent and moving to clinical trials in acute ischemic stroke.© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.

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