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Neuroscience Bulletin

, Volume 28, Issue 5, pp 499–508 | Cite as

Sevoflurane exposure in 7-day-old rats affects neurogenesis, neurodegeneration and neurocognitive function

  • Fang Fang
  • Zhanggang Xue
  • Jing CangEmail author
Original Article

Abstract

Objective

Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain. The present study was carried out to investigate the effects of sevoflurane on neurogenesis, neurodegeneration and behavior.

Methods

We administered 5-bromodeoxyuridine, an S-phase marker, before, during, and after 4 h of sevoflurane given to rats on postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade staining for degeneration. Spatial reference memory was tested 2 and 6 weeks after anesthesia.

Results

Sevo-flurane decreased progenitor proliferation and increased cell death until at least 4 days after anesthesia. Spatial reference memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane administration.

Conclusion

Sevoflurane reduces neurogenesis and increases the death of progenitor cells in developing brain. This might mediate the late-onset neurocognitive outcome after sevoflurane application.

Keywords

sevoflurane neurogenesis progenitor proliferation degeneration 

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References

  1. [1]
    Wise-Faberowski L, Zhang H, Ing R, Pearlstein RD, Warner DS. Isoflurane-induced neuronal degeneration: an evaluation in organotypic hippocampal slice cultures. Anesth Analg 2005, 101: 651–657.PubMedCrossRefGoogle Scholar
  2. [2]
    Young C, Jevtovic-Todorovic V, Qin YQ, Tenkova T, Wang H, Labruyere J, et al. Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol 2005, 146: 189–197.PubMedCrossRefGoogle Scholar
  3. [3]
    Olney JW, Ishimaru MJ, Bittigau P, Ikonomidou C. Ethanolinduced apoptotic neurodegeneration in the developing brain. Apoptosis 2000, 5: 515–521.PubMedCrossRefGoogle Scholar
  4. [4]
    Fredriksson A, Ponten E, Gordh T, Eriksson P. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology 2007, 107: 427–436.PubMedCrossRefGoogle Scholar
  5. [5]
    Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003, 23: 876–882.PubMedGoogle Scholar
  6. [6]
    Honegger P, Matthieu JM. Selective toxicity of the general anesthetic propofol for GABAergic neurons in rat brain cell cultures. J Neurosci Res 1996, 45: 631–636.PubMedCrossRefGoogle Scholar
  7. [7]
    Spahr-Schopfer I, Vutskits L, Toni N, Buchs PA, Parisi L, Muller D. Differential neurotoxic effects of propofol on dissociated cortical cells and organotypic hippocampal cultures. Anesthesiology 2000, 92: 1408–1417.PubMedCrossRefGoogle Scholar
  8. [8]
    Vutskits L, Gascon E, Tassonyi E, Kiss JZ. Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated gamma-aminobutyric acid-positive interneurons. Anesthesiology 2005, 102: 970–976.PubMedCrossRefGoogle Scholar
  9. [9]
    Bayer SA, Altman J, Russo RJ, Zhang X. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 1993, 14: 83–144.PubMedGoogle Scholar
  10. [10]
    Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev 1979, 3: 79–83.PubMedCrossRefGoogle Scholar
  11. [11]
    Olney JW, Tenkova T, Dikranian K, Qin YQ, Labruyere J, Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain. Brain Res Dev Brain Res 2002, 133: 115–126.PubMedCrossRefGoogle Scholar
  12. [12]
    Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000, 108 (Suppl 3): 511–533.PubMedGoogle Scholar
  13. [13]
    Stratmann G, Sall JW, May LD, Bell JS, Magnusson KR, Rau V, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology 2009, 110: 834–848.PubMedCrossRefGoogle Scholar
  14. [14]
    Satomoto M, Satoh Y, Terui K, Miyao H, Takishima K, Ito M, et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009, 110: 628–637.PubMedCrossRefGoogle Scholar
  15. [15]
    Altman J, Bayer SA. Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 1990, 301: 365–381.PubMedCrossRefGoogle Scholar
  16. [16]
    Madsen TM, Kristjansen PE, Bolwig TG, Wortwein G. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience 2003, 119: 635–642.PubMedCrossRefGoogle Scholar
  17. [17]
    Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 2004, 188: 316–330.PubMedCrossRefGoogle Scholar
  18. [18]
    Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994, 80: 814–824.PubMedCrossRefGoogle Scholar
  19. [19]
    Bercker S, Bert B, Bittigau P, Felderhoff-Muser U, Buhrer C, Ikonomidou C, et al. Neurodegeneration in newborn rats following propofol and sevoflurane anesthesia. Neurotox Res 2009, 16: 140–147.PubMedCrossRefGoogle Scholar
  20. [20]
    Bian M, Yu M, Yang S, Gao H, Huang Y, Deng C, et al. Expression of Cbl-interacting protein of 85 kDa in MPTP mouse model of Parkinson’s disease and 1-methyl-4-phenyl-pyridinium ion-treated dopaminergic SH-SY5Y cells. Acta Biochim Biophys Sin (Shanghai) 2008, 40: 505–5PubMedCrossRefGoogle Scholar
  21. [21]
    Kawakami Y, Yoshida K, Yang JH, Suzuki T, Azuma N, Sakai K, et al. Impaired neurogenesis in embryonic spinal cord of Phgdh knockout mice, a serine deficiency disorder model. Neurosci Res 2009, 63: 184–193.PubMedCrossRefGoogle Scholar
  22. [22]
    Livak KJ, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001, 25: 402–408.PubMedCrossRefGoogle Scholar
  23. [23]
    Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, et al. The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 2008, 64: 618–627.PubMedCrossRefGoogle Scholar
  24. [24]
    Schmued LC, Hopkins KJ. Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 2000, 874: 123–130.PubMedCrossRefGoogle Scholar
  25. [25]
    Ye X, Carp RI, Schmued LC, Scallet AC. Fluoro-Jade and silver methods: application to the neuropathology of scrapie, a transmissible spongiform encephalopathy. Brain Res Brain Res Protoc 2001, 8: 104–112.PubMedCrossRefGoogle Scholar
  26. [26]
    Schmued LC, Albertson C, Slikker W Jr. Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res Brain Res Rev 1997, 751: 37–46.Google Scholar
  27. [27]
    Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998, 281: 1312–1316.PubMedCrossRefGoogle Scholar
  28. [28]
    Keith JR, Wu Y, Epp JR, Sutherland RJ. Fluoxetine and the dentate gyrus: memory, recovery of function, and electrophysiology. Behav Pharmacol 2007, 18: 521–531.PubMedCrossRefGoogle Scholar
  29. [29]
    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000, 182: 311–322.PubMedCrossRefGoogle Scholar
  30. [30]
    Cameron HA, McKay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol 2001, 435: 406–417.PubMedCrossRefGoogle Scholar
  31. [31]
    Kee N, Teixeira CM, Wang AH, Frankland PW. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 2007, 10: 355–362.PubMedCrossRefGoogle Scholar
  32. [32]
    Kempermann G, Wiskott L, Gage FH. Functional significance of adult neurogenesis. Curr Opin Neurobiol 2004, 14: 186–191.PubMedCrossRefGoogle Scholar
  33. [33]
    Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000, 287: 1056–1060.PubMedCrossRefGoogle Scholar
  34. [34]
    Ikonomidou C, Bittigau P, Koch C, Genz K, Hoerster F, Felderhoff-Mueser U, et al. Neurotransmitters and apoptosis in the developing brain. Biochem Pharmacol 2001, 62: 401–405.PubMedCrossRefGoogle Scholar
  35. [35]
    Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999, 283: 70–74.PubMedCrossRefGoogle Scholar
  36. [36]
    Ishimaru MJ, Ikonomidou C, Tenkova TI, Der TC, Dikranian K, Sesma MA, et al. Distinguishing excitotoxic from apoptotic neurodegeneration in the developing rat brain. J Comp Neurol 1999, 408: 461–476.PubMedCrossRefGoogle Scholar
  37. [37]
    Sall JW, Stratmann G, Leong J, McKleroy W, Mason D, Shenoy S, et al. Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture. Anesthesiology 2009, 110: 826–833.PubMedCrossRefGoogle Scholar
  38. [38]
    D’Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 2001, 36: 60–90.PubMedCrossRefGoogle Scholar
  39. [39]
    Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 1997, 386: 493–495.PubMedCrossRefGoogle Scholar
  40. [40]
    Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A 1998, 95: 3168–3171.PubMedCrossRefGoogle Scholar
  41. [41]
    Zhu C, Gao J, Karlsson N, Li Q, Zhang Y, Huang Z, et al. Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents. J Cereb Blood Flow Metab 2010, 30: 1017–1030.PubMedCrossRefGoogle Scholar
  42. [42]
    Dupret D, Revest JM, Koehl M, Ichas F, De Giorgi F, Costet P, et al. Spatial relational memory requires hippocampal adult neurogenesis. PLoS One 2008, 3: e1959.PubMedCrossRefGoogle Scholar
  43. [43]
    Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E. Neurogenesis in the adult is involved in the formation of trace memories. Nature 2001, 410: 372–376.PubMedCrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Anesthesiology, Zhongshan HospitalFudan UniversityShanghaiChina

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