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Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain.

Abstract：

Background:Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. Methods:Six-day-old NHP infants ( Macaca mulatta ) were exposed to 3 h of a surgical plane of ISO ( n =6) or to room air ( n =5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. Results:ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm -3 vs 14 (SD 5.2) mm -3 , respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. Conclusions:A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

journal_name

Br J Anaesth

journal_title

British journal of anaesthesia

authors

Noguchi KK,Johnson SA,Dissen GA,Martin LD,Manzella FM,Schenning KJ,Olney JW,Brambrink AM

doi

10.1093/bja/aex123

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

524-531

issue

3

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)53769-1

journal_volume

119

pub_type

杂志文章

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