Xenon Upregulates Hypoxia Inducible Factor 1 Alpha in Neonatal Rat Brain under Normoxic Conditions

Simona Valleggi ； Chirag B. Patel ； Andrea O. Cavazzana ； Daqing Ma ； Francesco Giunta ； Davide Cattano

《ISRN Anesthesiology》 2011 (2011/12) Pp. 20-26

並列摘要

Xenon can induce cell and organ protection through different molecular mechanisms related to oxygen level. We explored the effect of xenon on oxygen-related signalling in the central nervous systemvia hypoxia inducible factor 1 alpha (HIF-1α) and mammalian target of rapamycin (mTOR). Methods. Postnatal day 7 (P7) Sprague Dawley rats were exposed to 25% oxygen/75% nitrogen (air group) or 25% oxygen/75% xenon (treatment group) for 120 min. Brains were collected immediately (transcript analysis-relative real-time polymerase chain reaction) or 24 hours (protein analysis-immunohistochemistry) after the 120-minute exposure period; peak anesthetic preconditioning has been previously identified at 24 hours post-exposure. Results. HIF-1α transcript and protein levels were found to be increased in xenon-exposed compared to air-exposed brains. Sustained nuclear translocation of the protein, accounting for an increased activity of HIF-1α, was also noted. mTOR transcript analysis revealed no significant difference between xenon-exposed and air-exposed brains immediately after the 120-minute exposure. Conclusion. Our data suggest that xenon induces the upregulation of HIF-1α transcription and translation, which may contribute to xenon's neuroprotective preconditioning effect. However, given that xenon exposure did not affect mTOR transcription, further investigation into other signalling cascades mediating xenon's effects on HIF-1α in developing brain is warranted.