Isoflurane Exposure Induces Cell Death, Microglial Activation and Modifies the Expression of Genes Supporting Neurodevelopment and Cognitive Function in the Male Newborn Piglet Brain.
Isoflurane Exposure Induces Cell Death, Microglial Activation and Modifies the Expression of Genes Supporting Neurodevelopment and Cognitive Function in the Male Newborn Piglet Brain.
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DOI：
10.1371/journal.pone.0166784
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Robertson NJ
中科院分区：
文献类型：
--
作者：
Broad KD;Hassell J;Fleiss B;Kawano G;Ezzati M;Rocha-Ferreira E;Hristova M;Bennett K;Fierens I;Burnett R;Chaban B;Alonso-Alconada D;Oliver-Taylor A;Tachsidis I;Rostami J;Gressens P;Sanders RD;Robertson NJ
婴儿早期全身麻醉可能会对大脑的神经和认知发育产生不利影响。调节这一过程的机制是复杂的、不完全了解的，可能是性二态的，但包括发育不适当的细胞凋亡、炎症和认知显著基因表达的中断。我们研究了异氟醚暴露6h对雄性新生仔猪脑细胞死亡、小胶质细胞激活和基因表达的影响。仔猪(n=6)随机分为：(I)单纯对照组或(Ii)6h异氟醚。在7个脑区记录细胞死亡(TUNEL和caspase-3)和小胶质细胞激活。评估扣带回皮质基因表达的变化(微阵列和qPCR)。全程记录脑电(EEG)。异氟醚麻醉引起扣带回和岛叶皮质、尾状核、丘脑、壳核、内囊、脑室周围白质和海马区细胞死亡显著增加。死亡细胞包括神经元和少突胶质细胞。脑岛、梨状核、海马体、内囊、尾状核和丘脑的小胶质细胞明显活化。异氟醚对79个基因转录本的表达产生显著干扰，其中26个对转录调控起重要作用，23个对神经可塑性、记忆形成和回忆起重要调节作用。我们的观察证实了异氟烷增加了新生仔猪大脑中的细胞凋亡和炎症反应，但也提示了新的额外机制，即异氟烷可能通过破坏介导神经回路活动依赖的发育、大脑的预测性适应性反应、记忆形成和回忆的基因的表达来诱导不利的神经和认知发育。
Exposure of the brain to general anesthesia during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex, incompletely understood and may be sexually dimorphic, but include developmentally inappropriate apoptosis, inflammation and a disruption to cognitively salient gene expression. We investigated the effects of a 6h isoflurane exposure on cell death, microglial activation and gene expression in the male neonatal piglet brain. Piglets (n = 6) were randomised to: (i) naive controls or (ii) 6h isoflurane. Cell death (TUNEL and caspase-3) and microglial activation were recorded in 7 brain regions. Changes in gene expression (microarray and qPCR) were assessed in the cingulate cortex. Electroencephalography (EEG) was recorded throughout. Isoflurane anesthesia induced significant increases in cell death in the cingulate and insular cortices, caudate nucleus, thalamus, putamen, internal capsule, periventricular white matter and hippocampus. Dying cells included both neurons and oligodendrocytes. Significantly, microglial activation was observed in the insula, pyriform, hippocampus, internal capsule, caudate and thalamus. Isoflurane induced significant disruption to the expression of 79 gene transcripts, of these 26 are important for the control of transcription and 23 are important for the mediation of neural plasticity, memory formation and recall. Our observations confirm that isoflurane increases apoptosis and inflammatory responses in the neonatal piglet brain but also suggests novel additional mechanisms by which isoflurane may induce adverse neural and cognitive development by disrupting the expression of genes mediating activity dependent development of neural circuits, the predictive adaptive responses of the brain, memory formation and recall.
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DOI：
10.1016/s0140-6736(15)00608-x
发表时间：
2016-01-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
Davidson AJ;Disma N;de Graaff JC;Withington DE;Dorris L;Bell G;Stargatt R;Bellinger DC;Schuster T;Arnup SJ;Hardy P;Hunt RW;Takagi MJ;Giribaldi G;Hartmann PL;Salvo I;Morton NS;von Ungern Sternberg BS;Locatelli BG;Wilton N;Lynn A;Thomas JJ;Polaner D;Bagshaw O;Szmuk P;Absalom AR;Frawley G;Berde C;Ormond GD;Marmor J;McCann ME;GAS consortium
通讯作者：
GAS consortium
影响因子：
3.1
作者：
Broad KD;Rocha-Ferreira E;Hristova M
通讯作者：
Hristova M
影响因子：
4.2
作者：
Bateson, Patrick
通讯作者：
Bateson, Patrick
影响因子：
9.8
作者：
Culley, D. J.;Cotran, E. K.;Crosby, G.
通讯作者：
Crosby, G.
影响因子：
5.7
作者：
DiMaggio C;Sun LS;Li G
通讯作者：
Li G