Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists.
Anesthesia with sevoflurane in neonatal rats: Developmental neuroendocrine abnormalities and alleviating effects of the corticosteroid and Cl(-) importer antagonists.
复制标题
DOI：
10.1016/j.psyneuen.2015.06.016
复制
发表时间：
2015-10
影响因子：
3.7
通讯作者：
Martynyuk AE
中科院分区：
文献类型：
--
作者：
Xu C;Tan S;Zhang J;Seubert CN;Gravenstein N;Sumners C;Vasilopoulos T;Martynyuk AE
1.5仅在美国，每年就有100万12个月以下的儿童接受全身麻醉。人类和特别是动物研究提供的证据表明，在出生后早期暴露于全身麻醉可能会导致长期的神经认知异常，其机制尚不清楚。我们研究了是否一个不成熟的应激反应系统和γ-氨基丁酸（GABA）A型受体活动参与介导这些异常。用2.1%七氟烷麻醉出生后第4、5或6天的Sprague-Dawley大鼠6小时;将与母体分离的大鼠和圈养大鼠作为对照。七氟烷麻醉显著增加两种性别大鼠幼仔的皮质酮水平。成年后，这些大鼠对压力的反应是皮质酮分泌增加，雄性大鼠的皮质酮水平比雌性大鼠增加得更多。仅先前暴露于新生儿七氟烷的雄性大鼠在CA 1神经元中具有更高频率的微型抑制性突触后电流，在高架十字迷宫（高架十字迷宫）的开放臂中花费的时间更短，并且表现出惊吓的前脉冲抑制（PPI）受损。在七氟烷给药前，用Na+-K+-2Cl−协同转运蛋白抑制剂布美他尼或盐皮质激素受体拮抗剂RU 28318对雄性大鼠进行预处理，可使成年期应激的内分泌反应和应激行为正常化，而只有用布美他尼预处理的雄性大鼠表现出正常的惊恐反应PPI。布美他尼和RU 28318均未改变七氟烷对突触活性的影响。麻醉时七氟烷增强的神经元兴奋和皮质类固醇水平升高有助于启动新生儿七氟烷诱导的长期内分泌和神经行为异常的机制。
1.5 million children under 12 months of age are exposed to general anesthesia annually in the United States alone. Human and especially animal studies provide evidence that exposure to general anesthesia during the early postnatal period may lead to long-term neurocognitive abnormalities via poorly understood mechanisms. We investigated whether an immature stress response system and γ-aminobutyric acid (GABA) type A receptor activities are involved in mediating these abnormalities. Sprague-Dawley rats at postnatal days 4, 5 or 6 were anesthetized with 2.1% sevoflurane for 6 hrs; maternally separated and house reared rats served as controls. Sevoflurane anesthesia markedly increased corticosterone levels in rat pups of both genders. In adulthood, these rats responded to stress with heightened secretion of corticosterone and a greater increase in corticosterone levels in males versus females. Only male rats, previously exposed to neonatal sevoflurane, had a higher frequency of miniature inhibitory postsynaptic currents in CA1 neurons, spent a shorter time in open arms of the elevated plus maze (EPM) and exhibited impaired prepulse inhibition (PPI) of startle. Pretreatment of male rats prior to sevoflurane with the Na+-K+-2Cl− cotransporter inhibitor, bumetanide, or the mineralocorticoid receptor antagonist, RU28318, normalized endocrine responses to stress and the EPM behavior in adulthood, while only those pretreated with bumetanide exhibited normalized PPI of startle responses. Neither bumetanide nor RU28318 altered the effect of sevoflurane on synaptic activity. Sevoflurane-enhanced neuronal excitation and elevated corticosteroid levels at the time of anesthesia contribute to the mechanisms initiating neonatal sevoflurane-induced long-term endocrine and neurobehavioral abnormalities.