Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain
Article first published online: 29 OCT 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 4, pages 525–535, October 2012
How to Cite
Brambrink, A. M., Back, S. A., Riddle, A., Gong, X., Moravec, M. D., Dissen, G. A., Creeley, C. E., Dikranian, K. T. and Olney, J. W. (2012), Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain. Ann Neurol., 72: 525–535. doi: 10.1002/ana.23652
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Accepted manuscript online: 13 JUN 2012 07:19AM EST
- Manuscript Accepted: 21 MAY 2012
- Manuscript Received: 29 NOV 2011
- National Institute of Child Health and Human Development. Grant Numbers: HD37100, HD 052664, HD 062171
- National Institute of Neurological Diseases and Stroke. Grant Numbers: 1RO1NS054044, R37NS045737-06S1/06S2, 1F30NS066704
- Bugher Award and Grant in Aid from the American Heart Association
- March of Dimes Birth Defects Foundation. Grant Number: RR-000163
- Oregon National Primate Research Center
Previously we reported that exposure of 6-day-old (P6) rhesus macaques to isoflurane for 5 hours triggers a robust neuroapoptosis response in developing brain. We have also observed (unpublished data) that isoflurane causes apoptosis of cellular profiles in the white matter that resemble glia. We analyzed the cellular identity of the apoptotic white matter profiles and determined the magnitude of this cell death response to isoflurane.
Neonatal (P6) rhesus macaques were exposed for 5 hours to isoflurane anesthesia according to current clinical standards in pediatric anesthesia. Brains were collected 3 hours later and examined immunohistochemically to analyze apoptotic neuronal and glial death.
Brains exposed to isoflurane displayed significant apoptosis in both the white and gray matter throughout the central nervous system. Approximately 52% of the dying cells were glia, and 48% were neurons. Oligodendrocytes (OLs) engaged in myelinogenesis were selectively vulnerable, in contrast to OL progenitors, astrocytes, microglia, and interstitial neurons. When adjusted for control rates of OL apoptosis, the percentage of OLs that degenerated in the forebrain white matter of the isoflurane-treated group was 6.3% of the total population of myelinating OLs.
Exposure of the infant rhesus macaque brain to isoflurane for 5 hours is sufficient to cause widespread apoptosis of neurons and OLs throughout the developing brain. Deletion of OLs at a stage when they are just beginning to myelinate axons could potentially have adverse long-term neurobehavioral consequences that might be additive to the potential consequences of isoflurane-induced neuroapoptosis. ANN NEUROL 2012;72:525–535