Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain.
Surgery increases cell death and induces changes in gene expression compared with anesthesia alone in the developing piglet brain.
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DOI：
10.1371/journal.pone.0173413
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发表时间：
2017
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;Kawano G;Fierens I;Rocha-Ferreira E;Hristova M;Ezzati M;Rostami J;Alonso-Alconada D;Chaban B;Hassell J;Fleiss B;Gressens P;Sanders RD;Robertson NJ
在一系列动物物种中，在婴儿早期将大脑暴露于全身麻醉而不进行手术可能会对其神经和认知发育产生不利影响。介导这一过程的机制很复杂，但包括脑细胞死亡的增加。在人类中，试图将不利的认知发展与婴儿麻醉暴露联系起来，结果模棱两可。可能影响人类研究解释的一个警告是，婴儿在没有手术的情况下不会暴露于全身麻醉，这增加了手术本身可能导致不良认知发育的可能性。使用小猪，我们调查了一个小手术是否会增加细胞死亡，并破坏新生儿大脑中的神经发育和认知显着基因转录。我们将新生雄性仔猪随机分配至接受6小时2%异氟烷麻醉的组或接受相同麻醉加15分钟手术的组，该手术旨在复制腹股沟疝修补术。与单纯麻醉相比，手术导致大脑八个区域的细胞死亡显著增加。使用来自每组所有12只小猪的RNAseq数据，我们还鉴定了扣带皮层中由手术诱导的181个基因转录物表达的显著变化，这些变化的通路分析表明手术影响凝血酶、醛固酮、轴突导向、B细胞、ERK-5、eNOS和GABAA信号传导通路。这表明了一些新的机制，手术可能会影响神经和认知发展独立或协同麻醉的影响。
In a range of animal species, exposure of the brain to general anaesthesia without surgery during early infancy may adversely affect its neural and cognitive development. The mechanisms mediating this are complex but include an increase in brain cell death. In humans, attempts to link adverse cognitive development to infantile anaesthesia exposure have yielded ambiguous results. One caveat that may influence the interpretation of human studies is that infants are not exposed to general anaesthesia without surgery, raising the possibility that surgery itself, may contribute to adverse cognitive development. Using piglets, we investigated whether a minor surgical procedure increases cell death and disrupts neuro-developmental and cognitively salient gene transcription in the neonatal brain. We randomly assigned neonatal male piglets to a group who received 6h of 2% isoflurane anaesthesia or a group who received an identical anaesthesia plus 15 mins of surgery designed to replicate an inguinal hernia repair. Compared to anesthesia alone, surgery-induced significant increases in cell death in eight areas of the brain. Using RNAseq data derived from all 12 piglets per group we also identified significant changes in the expression of 181 gene transcripts induced by surgery in the cingulate cortex, pathway analysis of these changes suggests that surgery influences the thrombin, aldosterone, axonal guidance, B cell, ERK-5, eNOS and GABAA signalling pathways. This suggests a number of novel mechanisms by which surgery may influence neural and cognitive development independently or synergistically with the effects of anaesthesia.