Dustin Johnsen1, Stephanie J Murphy. 1. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
Abstract
BACKGROUND: Isoflurane exposure can protect the mammalian brain from subsequent insults such as ischemic stroke. However, this protective preconditioning effect is sexually dimorphic, with isoflurane preconditioning decreasing male while exacerbating female brain damage in a mouse model of cerebral ischemia. Emerging evidence suggests that innate cell sex is an important factor in cell death, with brain cells having sex-specific sensitivities to different insults. We used an in vitro model of isoflurane preconditioning and ischemia to test the hypothesis that isoflurane preconditioning protects male astrocytes while having no effect or even a deleterious effect in female astrocytes after subsequent oxygen and glucose deprivation (OGD). METHODS: Sex-segregated astrocyte cultures derived from postnatal day 0 to 1 mice were allowed to reach confluency before being exposed to either 0% (sham preconditioning) or 3% isoflurane preconditioning for 2 hours. Cultures were then returned to normal growth conditions for 22 hours before undergoing 10 hours of OGD. Twenty-four hours after OGD, cell viability was quantified using a lactate dehydrogenase assay. RESULTS: Isoflurane preconditioning increased cell survival after OGD compared with sham preconditioning independent of innate cell sex. CONCLUSION: More studies are needed to determine how cell type and cell sex may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain.
BACKGROUND:Isoflurane exposure can protect the mammalian brain from subsequent insults such as ischemic stroke. However, this protective preconditioning effect is sexually dimorphic, with isoflurane preconditioning decreasing male while exacerbating female brain damage in a mouse model of cerebral ischemia. Emerging evidence suggests that innate cell sex is an important factor in cell death, with brain cells having sex-specific sensitivities to different insults. We used an in vitro model of isoflurane preconditioning and ischemia to test the hypothesis that isoflurane preconditioning protects male astrocytes while having no effect or even a deleterious effect in female astrocytes after subsequent oxygen and glucose deprivation (OGD). METHODS: Sex-segregated astrocyte cultures derived from postnatal day 0 to 1 mice were allowed to reach confluency before being exposed to either 0% (sham preconditioning) or 3% isoflurane preconditioning for 2 hours. Cultures were then returned to normal growth conditions for 22 hours before undergoing 10 hours of OGD. Twenty-four hours after OGD, cell viability was quantified using a lactate dehydrogenase assay. RESULTS:Isoflurane preconditioning increased cell survival after OGD compared with sham preconditioning independent of innate cell sex. CONCLUSION: More studies are needed to determine how cell type and cell sex may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain.
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