Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain

K. K. Noguchi, S. A. Johnson, Gregory Dissen, Lauren Drew Martin, F. M. Manzella, K. J. Schenning, J. W. Olney, Ansgar Brambrink

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Background: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. Methods: Six-day-old NHP infants (Macaca mulatta) were exposed to 3 h of a surgical plane of ISO (n=6) or to room air (n=5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. Results: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm â '3 vs 14 (SD 5.2) mm â '3, respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. Conclusions: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

    Original languageEnglish (US)
    Pages (from-to)524-531
    Number of pages8
    JournalBritish Journal of Anaesthesia
    Volume119
    Issue number3
    DOIs
    StatePublished - 2017

    Fingerprint

    Isoflurane
    Macaca
    Primates
    Cell Death
    Oligodendroglia
    Brain
    Apoptosis
    Anesthesia
    Putamen
    Clinical Medicine
    Macaca mulatta
    Thalamus
    Caspase 3
    Anesthetics
    Retrospective Studies
    Air
    Pediatrics
    Neurons
    Control Groups
    Research

    Keywords

    • anaesthesia
    • apoptosis
    • growth and development
    • isoflurane

    ASJC Scopus subject areas

    • Anesthesiology and Pain Medicine

    Cite this

    Noguchi, K. K., Johnson, S. A., Dissen, G., Martin, L. D., Manzella, F. M., Schenning, K. J., ... Brambrink, A. (2017). Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain. British Journal of Anaesthesia, 119(3), 524-531. https://doi.org/10.1093/bja/aex123

    Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain. / Noguchi, K. K.; Johnson, S. A.; Dissen, Gregory; Martin, Lauren Drew; Manzella, F. M.; Schenning, K. J.; Olney, J. W.; Brambrink, Ansgar.

    In: British Journal of Anaesthesia, Vol. 119, No. 3, 2017, p. 524-531.

    Research output: Contribution to journalArticle

    Noguchi, KK, Johnson, SA, Dissen, G, Martin, LD, Manzella, FM, Schenning, KJ, Olney, JW & Brambrink, A 2017, 'Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain', British Journal of Anaesthesia, vol. 119, no. 3, pp. 524-531. https://doi.org/10.1093/bja/aex123
    Noguchi, K. K. ; Johnson, S. A. ; Dissen, Gregory ; Martin, Lauren Drew ; Manzella, F. M. ; Schenning, K. J. ; Olney, J. W. ; Brambrink, Ansgar. / Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain. In: British Journal of Anaesthesia. 2017 ; Vol. 119, No. 3. pp. 524-531.
    @article{93a4e83844cc4282819f241adfceaa7b,
    title = "Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain",
    abstract = "Background: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. Methods: Six-day-old NHP infants (Macaca mulatta) were exposed to 3 h of a surgical plane of ISO (n=6) or to room air (n=5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. Results: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm {\^a} '3 vs 14 (SD 5.2) mm {\^a} '3, respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. Conclusions: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.",
    keywords = "anaesthesia, apoptosis, growth and development, isoflurane",
    author = "Noguchi, {K. K.} and Johnson, {S. A.} and Gregory Dissen and Martin, {Lauren Drew} and Manzella, {F. M.} and Schenning, {K. J.} and Olney, {J. W.} and Ansgar Brambrink",
    year = "2017",
    doi = "10.1093/bja/aex123",
    language = "English (US)",
    volume = "119",
    pages = "524--531",
    journal = "British Journal of Anaesthesia",
    issn = "0007-0912",
    publisher = "Oxford University Press",
    number = "3",

    }

    TY - JOUR

    T1 - Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain

    AU - Noguchi, K. K.

    AU - Johnson, S. A.

    AU - Dissen, Gregory

    AU - Martin, Lauren Drew

    AU - Manzella, F. M.

    AU - Schenning, K. J.

    AU - Olney, J. W.

    AU - Brambrink, Ansgar

    PY - 2017

    Y1 - 2017

    N2 - Background: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. Methods: Six-day-old NHP infants (Macaca mulatta) were exposed to 3 h of a surgical plane of ISO (n=6) or to room air (n=5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. Results: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm â '3 vs 14 (SD 5.2) mm â '3, respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. Conclusions: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

    AB - Background: Retrospective clinical studies suggest there is a risk for neurodevelopmental impairment following early childhood exposure to anaesthesia. In the developing animal brain, including those of non-human primates (NHPs), anaesthetics induce apoptotic cell death. We previously reported that a 5 h isoflurane (ISO) exposure in infant NHPs increases apoptosis 13-fold compared with control animals. However, the majority of paediatric surgeries requiring anaesthesia are of shorter durations. We examined whether 3 h ISO exposure similarly increases neuroapoptosis in the NHP developing brain. Methods: Six-day-old NHP infants (Macaca mulatta) were exposed to 3 h of a surgical plane of ISO (n=6) or to room air (n=5). Following exposure, NHP brains were screened for neuronal and oligodendrocyte apoptosis using activated caspase-3 immunolabelling and unbiased stereology. Results: ISO treatment increased apoptosis (neurones + oligodendrocyte) to greater than four times that in the control group [mean density of apoptotic profiles: 57 (SD 22) mm â '3 vs 14 (SD 5.2) mm â '3, respectively]. Oligodendrocyte apoptosis was evenly distributed throughout the white matter whereas neuroapoptosis occurred primarily in the cortex (all regions), caudate, putamen and thalamus. Conclusions: A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

    KW - anaesthesia

    KW - apoptosis

    KW - growth and development

    KW - isoflurane

    UR - http://www.scopus.com/inward/record.url?scp=85029818610&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85029818610&partnerID=8YFLogxK

    U2 - 10.1093/bja/aex123

    DO - 10.1093/bja/aex123

    M3 - Article

    C2 - 28969320

    AN - SCOPUS:85029818610

    VL - 119

    SP - 524

    EP - 531

    JO - British Journal of Anaesthesia

    JF - British Journal of Anaesthesia

    SN - 0007-0912

    IS - 3

    ER -