Previous studies have demonstrated that sevoflurane postconditioning can provide neuroprotection after hypoxic-ischemic injury and improve learning and memory function in developing rodent brains.The classical Rice-Va...Previous studies have demonstrated that sevoflurane postconditioning can provide neuroprotection after hypoxic-ischemic injury and improve learning and memory function in developing rodent brains.The classical Rice-Vannucci model was used to induce hypoxic-ischemic injury,and newborn(postnatal day 7)rats were treated with 2.4%sevoflurane for 30 minutes after hypoxic-ischemic injury.Our results showed that sevoflurane postconditioning significantly improved the learning and memory function of rats,decreased astrogliosis and glial scar formation,increased numbers of dendritic spines,and protected the histomorphology of the hippocampus.Mechanistically,sevoflurane postconditioning decreased expression of von Hippel-Lindau of hypoxia-inducible factor-1α and increased expression of DJ-1.Injection of 1.52μg of the hypoxia-inducible factor-1αinhibitor YC-1(Lificiguat)into the left lateral ventricle 30 minutes before hypoxic-ischemic injury reversed the neuroprotection induced by sevoflurane.This finding suggests that sevoflurane can effectively alleviate astrogliosis in the hippocampus and reduce learning and memory impairments caused by glial scar formation after hypoxic-ischemic injury.The underlying mechanism may be related to upregulated DJ-1 expression,reduced ubiquitination of hypoxia-inducible factor-1α,and stabilized hypoxiainducible factor-1αexpression.This study was approved by the Laboratory Animal Care Committee of China Medical University,China(approval No.2016PS337K)on November 9,2016.展开更多
基金supported by the National Nature Science Foundation of China,Nos.81671311,81870838the Key Research and Development Program of Liaoning Province of China,No.2018225004the Outstanding Scientific Fund of Shengjing Hospital of China,No.201708(all to PZ).
文摘Previous studies have demonstrated that sevoflurane postconditioning can provide neuroprotection after hypoxic-ischemic injury and improve learning and memory function in developing rodent brains.The classical Rice-Vannucci model was used to induce hypoxic-ischemic injury,and newborn(postnatal day 7)rats were treated with 2.4%sevoflurane for 30 minutes after hypoxic-ischemic injury.Our results showed that sevoflurane postconditioning significantly improved the learning and memory function of rats,decreased astrogliosis and glial scar formation,increased numbers of dendritic spines,and protected the histomorphology of the hippocampus.Mechanistically,sevoflurane postconditioning decreased expression of von Hippel-Lindau of hypoxia-inducible factor-1α and increased expression of DJ-1.Injection of 1.52μg of the hypoxia-inducible factor-1αinhibitor YC-1(Lificiguat)into the left lateral ventricle 30 minutes before hypoxic-ischemic injury reversed the neuroprotection induced by sevoflurane.This finding suggests that sevoflurane can effectively alleviate astrogliosis in the hippocampus and reduce learning and memory impairments caused by glial scar formation after hypoxic-ischemic injury.The underlying mechanism may be related to upregulated DJ-1 expression,reduced ubiquitination of hypoxia-inducible factor-1α,and stabilized hypoxiainducible factor-1αexpression.This study was approved by the Laboratory Animal Care Committee of China Medical University,China(approval No.2016PS337K)on November 9,2016.
