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Isoflurane‐induced apoptosis of oligodendrocytes in the neonatal primate brain
Author(s) -
Brambrink Ansgar M.,
Back Stephen A.,
Riddle Art,
Gong Xi,
Moravec Matthew D.,
Dissen Gregory A.,
Creeley Catherine E.,
Dikranian Krikor T.,
Olney John W.
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23652
Subject(s) - isoflurane , white matter , apoptosis , neuroscience , stereology , programmed cell death , medicine , population , macaque , biology , anesthesia , genetics , magnetic resonance imaging , environmental health , radiology
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 We have also observed (unpublished data) that isoflurane causes apoptosis of cellular profiles in the white matter that resemble glia.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