Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis

Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress....

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Main Authors: De-An Zhao, Ling-Yun Bi, Qian Huang, Fang-Min Zhang, Zi-Ming Han
Format: Article
Language:English
Published: Elsevier 2016-11-01
Series:Brazilian Journal of Anesthesiology
Online Access:http://www.sciencedirect.com/science/article/pii/S0104001416300628
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author De-An Zhao
Ling-Yun Bi
Qian Huang
Fang-Min Zhang
Zi-Ming Han
author_facet De-An Zhao
Ling-Yun Bi
Qian Huang
Fang-Min Zhang
Zi-Ming Han
author_sort De-An Zhao
collection DOAJ
description Background and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Resumo: Justificativa e objetivos: Isoflurano é um éter volátil halogenado usado para anestesia por via inalatória. É amplamente utilizado na clínica como um anestésico para inalação. A lesão hipóxico-isquêmica neonatal ocorre no cérebro imaturo e resulta em morte celular tardia via excitotoxicidade e estresse oxidativo. Isoflurano mostrou possuir propriedades neuroprotetoras que formam uma base benéfica para o seu uso tanto em cultura de células quanto em modelos animais, incluindo vários modelos de lesão cerebral. Nosso objetivo foi determinar o efeito neuroprotetor de isoflurano em hipóxia cerebral e elucidar o mecanismo subjacente. Métodos: Fatias de hipocampo, em fluido cerebrospinal artificial (CSFA) com glicose e privação de oxigênio, foram usadas como um modelo in vitro de hipóxia cerebral. O pico de população ortodrômica (PPO) e o potencial de lesão hipóxica (PLH) foram registrados nas regiões CA1 e CA3. A concentração de neurotransmissores de aminoácidos na solução de perfusão das fatias de hipocampo foi medida. Resultados: O tratamento com isoflurano retardou a eliminação do PPO e melhorou a recuperação do PPO; diminuiu a frequência do PLH, retardou o início do PLH e aumentou a duração do PLH. O tratamento com isoflurano também diminuiu a liberação de neurotransmissores de aminoácidos induzida pela hipóxia, como aspartato, glutamato e glicina, mas os níveis de ácido γ-aminobutírico (GABA) estavam elevados. Estudos morfológicos mostram que o tratamento de edema com isoflurano atenuou o edema de neurônios piramidais na região CA1. Também reduziu a apoptose, como mostrado pela expressão reduzida da caspase-3 e genes PARP. Conclusões: Isoflurano mostrou um efeito neuroprotetor na lesão neuronal no hipocampo induzida por hipóxia através da supressão de apoptose. Keywords: Isoflurane, Hippocampus, Brain injury, Neuroprotection, Apoptosis, Palavras-chave: Isoflurano, Hipocampo, Lesão cerebral, Neuroproteção, Apoptose
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spelling doaj.art-76928aa8228541daad57d4122b6c63d72022-12-22T04:32:50ZengElsevierBrazilian Journal of Anesthesiology0104-00142016-11-01666613621Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosisDe-An Zhao0Ling-Yun Bi1Qian Huang2Fang-Min Zhang3Zi-Ming Han4Corresponding author.; The First Affiliated Hospital of Xinxiang Medical University, Department of Pediatrics, Weihui, ChinaThe First Affiliated Hospital of Xinxiang Medical University, Department of Pediatrics, Weihui, ChinaThe First Affiliated Hospital of Xinxiang Medical University, Department of Pediatrics, Weihui, ChinaThe First Affiliated Hospital of Xinxiang Medical University, Department of Pediatrics, Weihui, ChinaThe First Affiliated Hospital of Xinxiang Medical University, Department of Pediatrics, Weihui, ChinaBackground and objectives: Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. Methods: A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Results: Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Conclusions: Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Resumo: Justificativa e objetivos: Isoflurano é um éter volátil halogenado usado para anestesia por via inalatória. É amplamente utilizado na clínica como um anestésico para inalação. A lesão hipóxico-isquêmica neonatal ocorre no cérebro imaturo e resulta em morte celular tardia via excitotoxicidade e estresse oxidativo. Isoflurano mostrou possuir propriedades neuroprotetoras que formam uma base benéfica para o seu uso tanto em cultura de células quanto em modelos animais, incluindo vários modelos de lesão cerebral. Nosso objetivo foi determinar o efeito neuroprotetor de isoflurano em hipóxia cerebral e elucidar o mecanismo subjacente. Métodos: Fatias de hipocampo, em fluido cerebrospinal artificial (CSFA) com glicose e privação de oxigênio, foram usadas como um modelo in vitro de hipóxia cerebral. O pico de população ortodrômica (PPO) e o potencial de lesão hipóxica (PLH) foram registrados nas regiões CA1 e CA3. A concentração de neurotransmissores de aminoácidos na solução de perfusão das fatias de hipocampo foi medida. Resultados: O tratamento com isoflurano retardou a eliminação do PPO e melhorou a recuperação do PPO; diminuiu a frequência do PLH, retardou o início do PLH e aumentou a duração do PLH. O tratamento com isoflurano também diminuiu a liberação de neurotransmissores de aminoácidos induzida pela hipóxia, como aspartato, glutamato e glicina, mas os níveis de ácido γ-aminobutírico (GABA) estavam elevados. Estudos morfológicos mostram que o tratamento de edema com isoflurano atenuou o edema de neurônios piramidais na região CA1. Também reduziu a apoptose, como mostrado pela expressão reduzida da caspase-3 e genes PARP. Conclusões: Isoflurano mostrou um efeito neuroprotetor na lesão neuronal no hipocampo induzida por hipóxia através da supressão de apoptose. Keywords: Isoflurane, Hippocampus, Brain injury, Neuroprotection, Apoptosis, Palavras-chave: Isoflurano, Hipocampo, Lesão cerebral, Neuroproteção, Apoptosehttp://www.sciencedirect.com/science/article/pii/S0104001416300628
spellingShingle De-An Zhao
Ling-Yun Bi
Qian Huang
Fang-Min Zhang
Zi-Ming Han
Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
Brazilian Journal of Anesthesiology
title Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
title_full Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
title_fullStr Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
title_full_unstemmed Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
title_short Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
title_sort isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis
url http://www.sciencedirect.com/science/article/pii/S0104001416300628
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AT fangminzhang isofluraneprovidesneuroprotectioninneonatalhypoxicischemicbraininjurybysuppressingapoptosis
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