Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome

Abstract

Objectives: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. Design: Controlled, randomized, double-blinded laboratory study. Setting: Animal research laboratories. Subjects: Adult Wistar male rats (n = 110). Interventions: Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed. Measurements and Main Results: After argon inhalation for 24 hours immediately following “severe permanent ischemia” induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed. Conclusions: Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.

Perioperative stroke: A perspective on challenges and opportunities for experimental treatment and diagnostic strategies

“…Argon reduces ischemic lesion size and improves functional outcome after 2 h of tMCAO, 80 and prolonged exposure of 24 h is safe in rodents. 81 Argon application is also safe in hemorrhagic stroke. Preclinical data are missing on PS, and argon was not yet applied clinically for NS stroke or PS.…”

Update of the organoprotective properties of xenon and argon: from bench to beside

“…These experiments did not lead to an improvement in neurologic outcome. Recently, Ma et al [114] proved that argon (70 Vol%) applied for 24 h in a MCAO model relevantly improved the neurologic outcome and reduced the final infarct volumes. Inflammation plays a major role after stroke by aggravating neuronal damage in the penumbra [86,115].…”

“…The microglia activation by ischaemia-reperfusion injury leads to an increase in oxidative stress, inflammation and apoptosis [118]. Ma et al applied argon (70%) for 24 h in a permanent MCAO model in rats onset 2 h after ischaemia [114]. In this model, infarct volume and 7-day mortality were not significantly reduced in argon-treated animals.…”

Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition

“…This more abundant gas extracted from air exerts anti-ischemic effects and provides promising experimental results in animal studies. These benefits have been mainly studied after regional ischemia with “single organ” dysfunction or after cardiac arrest for neuroprotective purpose [ 5 , 6 , 7 , 8 , 9 , 10 ]. Multiorgan protection was also reported by our group in a model of MOF induced by supra-coeliac aorta cross-clamping in rabbits [ 2 ].…”