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Anesthesiology. 2014 Mar;120(3):626-38. doi: 10.1097/ALN.0000000000000037.

Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal rhesus macaque brain.

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From the Department of Psychiatry (C.E.C., J.W.O.) and Department of Anatomy and Neurobiology (K.T.D.), Washington University School of Medicine, St. Louis, Missouri, and the Division of Neuroscience (G.A.D.) and Department of Anesthesiology and Perioperative Medicine (A.M.B.), Oregon National Primate Research Center, Portland, Orgeon, and the Department of Pediatrics (S.A.B.), Oregon Health and Science University, Portland, Oregon.



The authors have previously shown that exposure of the neonatal nonhuman primate (NHP) brain to isoflurane for 5 h causes widespread acute apoptotic degeneration of neurons and oligodendrocyte. The current study explored the potential apoptogenic action of isoflurane in the fetal NHP brain.


Fetal rhesus macaques at gestational age of 120 days (G120) were exposed in utero for 5 h to isoflurane anesthesia (n = 5) or to no anesthesia (control condition; n = 4), and all regions of the brain were systematically evaluated 3 h later for evidence of apoptotic degeneration of neurons or glia.


Exposure of the G120 fetal NHP brain to isoflurane caused a significant increase in apoptosis of neurons and of oligodendrocytes at a stage when oligodendrocytes were just beginning to myelinate axons. The neuroapoptosis response was most prominent in the cerebellum, caudate, putamen, amygdala, and several cerebrocortical regions. Oligodendrocyte apoptosis was diffusely distributed over many white matter regions. The total number of apoptotic profiles (neurons + oligodendrocytes) in the isoflurane-exposed brains was increased 4.1-fold, compared with the brains from drug-naive controls. The total number of oligodendrocytes deleted by isoflurane was higher than the number of neurons deleted.


Isoflurane anesthesia for 5 h causes death of neurons and oligodendrocytes in the G120 fetal NHP brain. In the fetal brain, as the authors previously found in the neonatal NHP brain, oligodendrocytes become vulnerable when they are just achieving myelination competence. The neurotoxic potential of isoflurane increases between the third trimester (G120) and the neonatal period in the NHP brain.

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