Xenon Confers Neuroprotection in Organotypic Hippocampal Slice Cultures

Abstract

Background: The present study sought to establish the use of a novel model of cerebral ischaemia in which to investigate the neuroprotective effects of xenon based on organotypic hippocampal slice cultures. Methods: Organotypic hippocampal slices, derived from 7-10 days post-natal C57B16 mouse pups, were placed and cultured for 10-14 days on membranous inserts. Neuronal injury of cultures was provoked with media deprived with oxygen and glucose (OGD) for 2 hours. Cultures were exposed to 25% xenon or 50% xenon and 20% oxygen and 5% carbon dioxide (CO2) balanced with nitrogen (N2) 24 hours before OGD insult (preconditioning) for 2 hours or 75% xenon and 5% CO2 balanced with oxygen 4 hours after OGD for 2 hours. Cell death was quantified by assessment of propidium iodide (PI) uptake before and after OGD up to 72 hours in the CA1 and the dentate gyrus (DG) of the hippocampus. Results: Xenon preconditioning at concentrations of 25% and 50% resulted in a significant reduction in PI uptake in the CA1 region of the hippocampus compared with the control group (P<0.01). The effect was less pronounced in the DG region with xenon only at a concentration of 25% (P<0.05). Xenon 75% treatment 4 hours postinsult significantly attenuated cell death in both the DG and CA1 areas of the hippocampus. Conclusions: This study corroborated previous data to confirm that xenon is a potent neuroprotectant, and advocated its potential for future use in specific clinical settings.