Isoflurane‐induced apoptosis of oligodendrocytes in the neonatal primate brain
Open accessAbstract
Objective: 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 We have also observed (unpublished data) that isoflurane causes apoptosis of cellular profiles in the white matter that resemble glia.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. Methods: 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. Results: 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. Interpretation: 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
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General anesthetics and alcohol reportedly caused apoptotic death mainly in neurons and oligodendrocytes, but not in astrocytes.
“Similarly, general anesthetics and alcohol reportedly caused apoptotic death mainly in neurons and oligodendrocytes, but not in astrocytes1718.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [17]
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- Authors
- Brambrink, A. M., Back, S. A., Riddle, A., Gong, X., Moravec, M. D., Dissen, G. A., Creeley, C. E., Dikranian, K. T., & Olney, J. W.
- Affiliations
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- Washington University in St. Louis (US)
- Corresponding author
- Brambrink, Ansgar M.
- Back, Stephen A.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-10
- Volume
- 72
- Issue
- 4
- Pages
- 525-535
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3490441
- OpenAlex
- W2158426552
- Cited by
- 264
- References
- 51
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 16 · 2021: 12 · 2020: 25 · 2019: 23 · 2018: 26 · 2017: 31 · 2016: 21 · 2015: 19 · 2014: 27 · 2013: 18 · 2012: 2
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS045737, R37NS045737-06S1/06S2, R01NS054044, R37NS045737, F30NS066704)
- National Center for Research Resources (RR000163, P51RR000163, K01RR000163)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 062171, R37HD037100, R01HD052664, HD052664, R01HD037100, P30HD062171, HD 37100)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- isoflurane, oligodendrocyte apoptosis, neonatal brain, rhesus monkeys, neuronal apoptosis, white matter, myelination, glial cell death, pediatric anesthesia, brain development, astrocytes, microglia
- MeSH terms
- Animals, Animals, Newborn, Axons, Brain, Immunohistochemistry, Isoflurane, Macaca mulatta, Myelin Sheath, Nerve Regeneration, Oligodendroglia, Tissue Fixation, Cell Death, Apoptosis, Anesthetics, Inhalation, Caspases
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