title: Isoflurane exposure leads to apoptosis of neurons and oligodendrocytes in 20- and 40-day old rhesus macaques.
abstract: Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt to further describe the window of vulnerability to anesthetic neurotoxicity, we exposed P20 and P40 rhesus macaques to 5h of isoflurane anesthesia or no exposure (control animals). Brains were collected 3h later and examined immunohistochemically to analyze neuronal and glial apoptosis. Brains exposed to isoflurane displayed neuron and oligodendrocyte apoptosis distributed throughout cortex and white matter, respectively. When combining the two age groups (P20+P40), the animals exposed to isoflurane had 3.6 times as many apoptotic cells as the control animals. In the isoflurane group, approximately 66% of the apoptotic cells were oligodendrocytes and 34% were neurons. In comparison, in our previous studies on P6 rhesus macaques, approximately 52% of the dying cells were glia and 48% were neurons. In conclusion, the present data suggest that the window of vulnerability for neurons is beginning to close in the P20 and P40 rhesus macaques, but continuing for oligodendrocytes.
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, 3181 SW Sam Jackson Park Road, Mail Code L459, OR 97239, United States. Electronic address: malcore@ohsu.edu.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Schenning
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box #8134, St. Louis, MO 63110, United States. Electronic address: noguchik@psychiatry.wustl.edu.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Noguchi
authors.affiliation: Division of Comparative Medicine, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, United States. Electronic address: martilau@ohsu.edu.
authors.forename: Lauren Drew
authors.initials: LD
authors.lastname: Martin
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box #8134, St. Louis, MO 63110, United States. Electronic address: fmanzell@gmail.com.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Manzella
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box #8134, St. Louis, MO 63110, United States. Electronic address: omar.cabrera@ucdenver.edu.
authors.forename: Omar H
authors.initials: OH
authors.lastname: Cabrera
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, United States. Electronic address: disseng@ohsu.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Dissen
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, 3181 SW Sam Jackson Park Road, Mail Code L459, OR 97239, United States. Electronic address: brambrin@ohsu.edu.
authors.forename: Ansgar M
authors.initials: AM
authors.lastname: Brambrink
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D005260:Female; D007530:Isoflurane / Q000009:adverse effects*; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*
chemical_list: D007530:Isoflurane
keywords: Apoptosis; Developmental anesthesia neurotoxicity; Isoflurane; Nonhuman primates; Pediatric anesthesia