Argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke

Abstract

Background: Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present study was to confirm a potential neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke as an essential step before considering the use of argon as a neuroprotective agent in humans. Methods: Thirteen adult monkeys (Macaca mulatta) were allocated to two groups: a control group (n=8) without neuroprotection and an argon group (n=5) in which argon inhalation (90 min) was initiated 30 minutes after onset of ischemia. Animals in both groups underwent brain MRI (pre-ischemic) at least 7 days before the intervention. The monkeys were subjected to focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). After tMCAO, MRI was performed 1 hour after cerebral reperfusion. The ischemic core volume was defined by the apparent diffusion coefficient (aDC) and edema in fluid attenuated inversion recovery (FLAIR) acquisitions. MRI masks were applied to distinguish between cortical and subcortical abnormalities. In addition, a modified version of the Rankin scale was used to neurologically assess post-tMCAO. Results: Despite variability in the ischemic core and edema volumes in the control group, argon significantly reduced ischemic core volume after ischemia compared to the control group (1.1 - 1.6 cm3 vs. 8.5 - 8.1 cm3; p=0.03). This effect was limited to cortical structures (0.6 - 1.1 cm3 vs. 7.4 - 7.2 cm3; p=0.03). No significant differences were observed in the edema volumes. Measures of neurological clinical outcome suggested a better prognosis in argon-treated animals. Conclusions: In the tMCAO macaque model, argon induced effective neuroprotective effects, leading to a reduced ischemic core in cortical areas. These results support the potential use of this therapeutic approach for future clinical studies in stroke patients.