Neither Xenon nor Fentanyl Induces Neuroapoptosis in the Newborn Pig Brain
Neither Xenon nor Fentanyl Induces Neuroapoptosis in the Newborn Pig Brain
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DOI：
10.1097/aln.0b013e318294934d
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发表时间：
2013-08-01
期刊：
影响因子：
8.8
通讯作者：
Thoresen, Marianne
中科院分区：
文献类型：
--
作者：
Sabir, Hemmen;Bishop, Sarah;Thoresen, Marianne
背景：一些吸入麻醉剂会增加发育中的大脑中凋亡细胞的死亡。在新生动物缺氧缺血性脑损伤后，氙气（一种吸入麻醉剂）与低温治疗相结合可增强神经保护作用。因此，作者检查了在常温或低温下，新生猪呼吸50%氙气并连续芬太尼镇静24小时是否有任何神经凋亡作用。方法：将26头小于24 h的健康猪随机分为4组：(1)低温条件下吸入50%芬太尼氙气24 h （Trec = 33.5℃），(2)常温条件下吸入50%芬太尼氙气24 h （Trec = 38.5℃），(3)常温条件下吸入芬太尼24 h，(4)常温条件下不通气的幼猪对照组。另外5只非随机的猪在常温下吸入2%异氟醚24小时，以验证吸入麻醉剂在我们模型中的促凋亡作用。病理细胞在皮层、壳核、海马、丘脑和白质中进行形态学评估。为了量化结果，免疫染色细胞（caspase-3和末端脱氧核苷酸转移酶介导的脱氧尿苷-三磷酸镍端标记）在相同的大脑区域进行计数。结果：(1)~(4)组各脑区凋亡细胞总数均小于5个，为正常发育的神经细胞凋亡。免疫染色和细胞计数后，回归分析显示50%氙气加芬太尼和单独芬太尼均未增加神经细胞凋亡。异氟醚导致免疫染色细胞平均增加5- 10倍。结论：在常温或低温条件下，吸入50%氙气24 h联合芬太尼镇静或芬太尼单独镇静均未引起新生猪脑神经细胞凋亡。呼吸2%异氟醚增加新生猪神经细胞凋亡。
Background: Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs.Methods: Twenty-six healthy pigs (< 24-h old) were randomized into four groups: (1) 24 h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 degrees C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 degrees C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions.Results: For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5-to 10-fold increase of immunostained cells.Conclusion: At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.