Delayed post-ischaemic administration of xenon reduces brain damage in a rat model of global ischaemia

Objective: Xenon and nitrous oxide have been shown to be neuroprotective in vivo and in vitro, but mainly in models of focal cerebral ischaemia. This study aimed to investigate whether the two gases are able to attenuate cerebral injury after global cerebral ischaemia. Methods: Adult male Wistar rats underwent bilateral common carotid artery occlusion and were ventilated for 1 hour with 21% O-2/78% N-2. They were then randomized to three groups which continued to receive atmospheric air, 50% N2O/50% O-2 and 50% Xe/50% O-2 for an additional period of 45 minutes. The number of ischaemic neurons, the cortical volume loss and the immunochemical and molecular expression of c-fos and MMP-9 were evaluated. Results: Xenon reduced the number of ischaemic neurons in the cortex and CA1 hippocampal region (p < 0.001) and decreased the cortical volume loss (p < 0.01). Immunochemical induction of c-fos in the cortex was significantly suppressed (p < 0.01) after administration of xenon. The molecular analysis revealed significant effects of N2O and xenon administration on c-fos and MMP-9 expression. Conclusions: The data indicate that N2O and xenon administration is neuroprotective 1 hour after bilateral common carotid artery occlusion. These findings provide valuable evidence on the beneficial role of N2O and xenon in global cerebral injury.