Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain.
Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain.
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DOI：
10.1097/aln.0b013e318242b2cd
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发表时间：
2012-02
期刊：
影响因子：
8.8
通讯作者：
Olney JW
中科院分区：
文献类型：
--
作者：
Brambrink AM;Evers AS;Avidan MS;Farber NB;Smith DJ;Martin LD;Dissen GA;Creeley CE;Olney JW
恒河猴胎儿暴露于氯胺酮麻醉24小时或新生儿暴露于氯胺酮麻醉9小时可导致发育中的大脑神经细胞凋亡。本研究进一步阐明了氯胺酮诱导恒河猴胎儿和新生儿神经细胞凋亡所需的最低暴露量，以及氯胺酮诱导神经细胞凋亡的程度和空间分布。氯胺酮通过静脉输注给予出生后第6天的恒河猴新生儿或妊娠120天（足月= 165天）的妊娠恒河猴雌性5 h。3小时后，通过剖腹产分娩胎儿，并研究胎儿和新生儿脑的凋亡神经变性的证据，如通过活化的半胱天冬酶-3染色所确定的。与未用药对照组（胎儿n = 4;新生儿n = 5）相比，暴露于氯胺酮的胎儿（n = 3）和新生儿（n = 4）脑细胞凋亡谱均显著增加。胎儿中氯胺酮暴露导致的神经元损失是新生儿的2.2倍。胎儿的神经变性模式与新生儿不同，在任一年龄段暴露的所有受试者都具有该年龄段的特征模式。发育中的恒河猴大脑在胎儿和新生儿年龄时对氯胺酮的致凋亡作用敏感，5 h的暴露持续时间足以在任一年龄诱导显著的神经细胞凋亡反应。氯胺酮在胎儿中诱导的神经退行性变模式与新生儿不同，胎儿大脑中因氯胺酮暴露而导致的神经元损失是新生儿大脑的2.2倍。
Exposure of rhesus macaque fetuses for 24 h, or neonates for 9 h, to ketamine anesthesia causes neuroapoptosis in the developing brain. The present study further clarifies the minimum exposure required for, and the extent and spatial distribution of, ketamine-induced neuroapoptosis in rhesus fetuses and neonates. Ketamine was administered by intravenous infusion for 5 h to postnatal day 6 rhesus neonates, or to pregnant rhesus females at 120 days gestation (full term = 165 days). Three hours later, fetuses were delivered by caesarian section, and the fetal and neonatal brains were studied for evidence of apoptotic neurodegeneration, as determined by activated caspase-3 staining. Both the fetal (n = 3) and neonatal (n = 4) ketamine-exposed brains had a significant increase in apoptotic profiles compared to drug-naive controls (fetal n = 4; neonatal n = 5). Loss of neurons due to ketamine exposure was 2.2 times greater in fetuses than in neonates. The pattern of neurodegeneration in fetuses was different from that in neonates, and all subjects exposed at either age had a pattern characteristic for that age. The developing rhesus macaque brain is sensitive to the apoptogenic action of ketamine at both a fetal and neonatal age, and exposure duration of 5 h is sufficient to induce a significant neuroapoptosis response at either age. The pattern of neurodegeneration induced by ketamine in fetuses was different from that in neonates, and loss of neurons attributable to ketamine exposure was 2.2 times greater in the fetal than neonatal brains.