Long lasting argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke

Abstract

In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke. Thirteen adult Macaca mulatta were subjected to a focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). The monkeys were randomly allocated to a control group (n = 8) and an argon group (n = 5). Pre-mixed gas (40–60 oxygen-argon) was applied 30 min after the onset of tMCAO to 30 min after reperfusion. Infarct volumes were measured from the MRI scans conducted 1 hour and 1 month after the reperfusion. A clinical neurological assessment was performed 24 hours and 1 month after tMCAO. Our results show that Argon dramatically reduced ischemic core volume after ischemia compared to the control group with a long-lasting improvement of post-stroke infarct volume at 1 month. In addition, the neurological scale suggests a better prognosis in argon-treated animals without reaching the significance threshold. These pre-clinical results in gyrencephalic non-human primates support the potential use of this therapeutic approach for future clinical studies.