Background Brief isoflurane anesthesia induces neuroapoptosis in the developing rodent brain, but susceptibility of nonhuman primates to the apoptogenic action of isoflurane has not been studied. Therefore, we exposed postnatal day 6 (P6) rhesus macaques to a surgical plane of isoflurane anesthesia for 5 h, and studied the brains 3 h later for histopathological changes. Method With the same intensity of physiological monitoring typical for human neonatal anesthesia, five P6 rhesus macaques were exposed for 5 h to isoflurane maintained between 0.7 and 1.5 end tidal Vol% (endotracheally intubated, mechanically ventilated), and five controls were exposed for 5 h to room air without further intervention. Three hours later, the brains were harvested and serially sectioned across the entire forebrain and midbrain, and stained immunohistochemically with antibodies to activated caspase-3 for detection and quantification of apoptotic neurons. Results Quantitative evaluation of brain sections revealed a median of 32.5 (range, 18.0 to 48.2) apoptotic cells per mm3 of brain tissue in the isoflurane group and only 2.5 (range, 1.9 to 3.8) in the control group (difference significant at p = 0.008). Apoptotic neuronal profiles were largely confined to the cerebral cortex. In the control brains, they were sparse and randomly distributed, whereas in the isoflurane brains they were abundant and preferentially concentrated in specific cortical layers and regions. Conclusion The developing nonhuman primate brain is sensitive to the apoptogenic action of isoflurane, and displays a 13-fold increase in neuroapoptosis after 5 h exposure to a surgical plane of isoflurane anesthesia.

Propofol anaesthesia for 5 h caused death of neurones and OLs in both the fetal and neonatal NHP brain. OLs become vulnerable to the apoptogenic action of propofol when they are beginning to achieve myelination competence.

Background 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. Method 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. Results 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. Conclusion 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.