Xenon preconditioning confers neuroprotection regardless of gender in a mouse model of transient middle cerebral artery occlusion.

Abstract

Xenon preconditioning induces tolerance to the consequences of an injurious stimulus such as cerebral ischaemia. There have been surprisingly few studies investigating gender difference in the efficacy of pharmacological preconditioning, despite the known ability of oestradiol to exert neuroprotectant activity. We explored this paradigm using a mouse model of transient middle cerebral artery occlusion. C57BL/6 mice both male and female received either 2 h of 70% xenon (preconditioning) or 70% nitrogen (control) balanced with oxygen. Twenty-four hours later animals underwent 1 h of middle cerebral artery occlusion and then allowed to recover. After a further 24 h, functional neurological outcome and cerebral infarct size were evaluated. Western blotting was used to detect activity of signalling pathways involving hypoxia-inducible factor (HIF)-1alpha and phospho-Akt for the preconditioning effect. Both xenon preconditioned male and females showed improved functional outcome on focal deficit scales (P<0.05). Cerebral infarct volumes were significantly reduced in both xenon treated male and females (P<0.01). There was no significant difference between the male and female cohorts. HIF-1alpha and phospho-Akt were quantitatively upregulated in both sexes. Our data suggested that xenon preconditioning improved histological and neurological functional outcome in both gender in a stroke model of mice.