Jeffrey T Young1, Roza M Vlasova2, Brittany R Howell3, Rebecca C Knickmeyer4, Elyse Morin3, Kaela I Kuitchoua3, Gabriele R Lubach5, Jean Noel4, Xiaoping Hu6, Yundi Shi4, Gibson Caudill4, Andrew L Alexander7, Marc Niethammer8, Merle G Paule9, Christopher L Coe5, Mar Sanchez10, Martin Styner1. 1. Department of Psychiatry University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 2. Department of Psychiatry University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: roza_vlasova@med.unc.edu. 3. Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. 4. Department of Psychiatry University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 5. Harlow Center for Biological Psychology, University of Wisconsin-Madison, Madison, WI, USA. 6. Department of Bioengineering, University of California, Riverside, CA, USA. 7. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA. 8. Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 9. Division of Neurotoxicology, National Center for Toxicological Research, US Food & Drug Administration, Jefferson, AR, USA. 10. Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
Abstract
BACKGROUND: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. METHODS: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. RESULTS: Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. CONCLUSIONS: Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.
BACKGROUND: Non-human primates are commonly used in neuroimaging research for which general anaesthesia or sedation is typically required for data acquisition. In this analysis, the cumulative effects of exposure to ketamine, Telazol® (tiletamine and zolazepam), and the inhaled anaesthetic isoflurane on early brain development were evaluated in two independent cohorts of typically developing rhesus macaques. METHODS: Diffusion MRI scans were analysed from 43 rhesus macaques (20 females and 23 males) at either 12 or 18 months of age from two separate primate colonies. RESULTS: Significant, widespread reductions in fractional anisotropy with corresponding increased axial, mean, and radial diffusivity were observed across the brain as a result of repeated anaesthesia exposures. These effects were dose dependent and remained after accounting for age and sex at time of exposure in a generalised linear model. Decreases of up to 40% in fractional anisotropy were detected in some brain regions. CONCLUSIONS: Multiple exposures to commonly used anaesthetics were associated with marked changes in white matter microstructure. This study is amongst the first to examine clinically relevant anaesthesia exposures on the developing primate brain. It will be important to examine if, or to what degree, the maturing brain can recover from these white matter changes.
Authors: Robert I Block; Joss J Thomas; Emine O Bayman; James Y Choi; Karolie K Kimble; Michael M Todd Journal: Anesthesiology Date: 2012-09 Impact factor: 7.892
Authors: Sarah J Short; Jed T Elison; Barbara Davis Goldman; Martin Styner; Hongbin Gu; Mark Connelly; Eric Maltbie; Sandra Woolson; Weili Lin; Guido Gerig; J Steven Reznick; John H Gilmore Journal: Neuroimage Date: 2012-09-16 Impact factor: 6.556
Authors: Brittany R Howell; Matthew S McMurray; Dora B Guzman; Govind Nair; Yundi Shi; Kai M McCormack; Xiaoping Hu; Martin A Styner; Mar M Sanchez Journal: Soc Neurosci Date: 2016-06-27 Impact factor: 2.083
Authors: Sean C L Deoni; Jonathan O'Muircheartaigh; Jed T Elison; Lindsay Walker; Ellen Doernberg; Nicole Waskiewicz; Holly Dirks; Irene Piryatinsky; Doug C Dean; N L Jumbe Journal: Brain Struct Funct Date: 2014-11-29 Impact factor: 3.270