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Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain.

Annals of neurology | Oct 30, 2012

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 We have also observed (unpublished data) that isoflurane causes apoptosis of cellular profiles in the white matter that resemble glia.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.

Pubmed ID: 23109147 RIS Download

Mesh terms: Anesthetics, Inhalation | Animals | Animals, Newborn | Apoptosis | Axons | Brain | Caspases | Cell Death | Immunohistochemistry | Isoflurane | Macaca mulatta | Myelin Sheath | Nerve Regeneration | Oligodendroglia | Tissue Fixation

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS054044
  • Agency: NICHD NIH HHS, Id: HD 062171
  • Agency: NICHD NIH HHS, Id: R01 HD052664
  • Agency: NINDS NIH HHS, Id: F30 NS066704
  • Agency: NICHD NIH HHS, Id: R01 HD037100
  • Agency: NCRR NIH HHS, Id: P51 RR000163
  • Agency: NICHD NIH HHS, Id: P30 HD062171
  • Agency: NINDS NIH HHS, Id: 1F30NS066704
  • Agency: NICHD NIH HHS, Id: HD 052664
  • Agency: NCRR NIH HHS, Id: RR-000163
  • Agency: NINDS NIH HHS, Id: 1R01NS054044
  • Agency: NCRR NIH HHS, Id: K01 RR000163
  • Agency: NINDS NIH HHS, Id: R37NS045737-06S1/06S2
  • Agency: NINDS NIH HHS, Id: R01 NS045737
  • Agency: NICHD NIH HHS, Id: R37 HD037100
  • Agency: NICHD NIH HHS, Id: HD37100
  • Agency: NINDS NIH HHS, Id: R37 NS045737

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