Efficacy of Rutin in Inhibiting Neuronal Apoptosis and Cognitive Disturbances in Sevoflurane or Propofol Exposed Neonatal Mice

Overview

Journal Int J Clin Exp Med

Specialty General Medicine

Date 2015 Nov 10

PMID 26550427

Citations 9

Authors

Yi-Gang Man

Rui-Gang Zhou

Bing Zhao

Affiliations

Soon will be listed here.

Abstract

Sevoflurane and propofol are widely used in pediatric anesthesia. Neurotoxicity of sevoflurane and propofol in developing brain has been reported and these effects raise concerns on the usage of the drugs. We investigated the influence of rutin, a flavonoid on the neurodegenerative effects of sevoflurane and propofol and on memory and cognition in neonatal rodent model. Separate groups of neonatal mice (C57BL/6) were administered with rutin at 25 or 50 mg/kg body weight (b.wt) from post natal day 2 (P1) to P21. P7 mice were exposed to 2.9% sevoflurane and/or propofol (150 mg/kg b.wt). Neuroapoptosis was assessed by measuring activated caspase-3 and by Fluoro-Jade C staining. Plasma S100β levels were detected by ELISA. Morris water maze test was performed to test learning and memory impairments in the animals. General behaviour of the mice was also assessed. Anesthesia exposure caused severe neuroapoptosis and also raised the levels of plasma S100β. Neuroapoptosis, memory and cognitive deficits observed following anesthetics were comparatively more profound in mice on exposure to combined drug (sevoflurane and propofol) than in those exposed to either of the anesthetics. Rutin at both the doses was effective in reducing the apoptotic cell counts and enhanced the memory and cognitive abilities. Rutin supplementation offered significant protection against anesthetic induced neurodegeneration and learning and memory disturbances.

Citing Articles

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Relevance of experimental paradigms of anesthesia induced neurotoxicity in the mouse.

Johnson S, Pan A, Sun G, Freed A, Stokes J, Bornstein R PLoS One. 2019; 14(3):e0213543.

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Repeated neonatal isoflurane exposures in the mouse induce apoptotic degenerative changes in the brain and relatively mild long-term behavioral deficits.

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Neurotoxicity of anesthetics: Mechanisms and meaning from mouse intervention studies.

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References

DHooge R, De Deyn P . Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev. 2001; 36(1):60-90. DOI: 10.1016/s0165-0173(01)00067-4. View

Brambrink A, Evers A, Avidan M, Farber N, Smith D, Zhang X . Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology. 2010; 112(4):834-41. PMC: 3962067. DOI: 10.1097/ALN.0b013e3181d049cd. View

Cattano D, Young C, Straiko M, Olney J . Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008; 106(6):1712-4. DOI: 10.1213/ane.0b013e318172ba0a. View

Wei H, Liang G, Yang H, Wang Q, Hawkins B, Madesh M . The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology. 2008; 108(2):251-60. DOI: 10.1097/01.anes.0000299435.59242.0e. View

Istaphanous G, Howard J, Nan X, Hughes E, McCann J, McAuliffe J . Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology. 2011; 114(3):578-87. DOI: 10.1097/ALN.0b013e3182084a70. View

Pearn M, Hu Y, Niesman I, Patel H, Drummond J, Roth D . Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology. 2011; 116(2):352-61. PMC: 3275822. DOI: 10.1097/ALN.0b013e318242a48c. View

Istaphanous G, Ward C, Nan X, Hughes E, McCann J, McAuliffe J . Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex. Anesth Analg. 2013; 116(4):845-54. DOI: 10.1213/ANE.0b013e318281e988. View

Saxe M, Battaglia F, Wang J, Malleret G, David D, Monckton J . Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A. 2006; 103(46):17501-6. PMC: 1859958. DOI: 10.1073/pnas.0607207103. View

Brambrink A, Evers A, Avidan M, Farber N, Smith D, Martin L . Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain. Anesthesiology. 2012; 116(2):372-84. PMC: 3433282. DOI: 10.1097/ALN.0b013e318242b2cd. View

10.

Lunardi N, Ori C, Erisir A, Jevtovic-Todorovic V . General anesthesia causes long-lasting disturbances in the ultrastructural properties of developing synapses in young rats. Neurotox Res. 2009; 17(2):179-88. PMC: 3629551. DOI: 10.1007/s12640-009-9088-z. View

11.

Bai T, Dong D, Pei L . Resveratrol mitigates isoflurane-induced neuroapoptosis by inhibiting the activation of the Akt-regulated mitochondrial apoptotic signaling pathway. Int J Mol Med. 2013; 32(4):819-26. DOI: 10.3892/ijmm.2013.1464. View

12.

Nothlings U, Murphy S, Wilkens L, Henderson B, Kolonel L . Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am J Epidemiol. 2007; 166(8):924-31. DOI: 10.1093/aje/kwm172. View

13.

Stratmann G . Review article: Neurotoxicity of anesthetic drugs in the developing brain. Anesth Analg. 2011; 113(5):1170-9. DOI: 10.1213/ANE.0b013e318232066c. View

14.

Flick R, Katusic S, Colligan R, Wilder R, Voigt R, Olson M . Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics. 2011; 128(5):e1053-61. PMC: 3307194. DOI: 10.1542/peds.2011-0351. View

15.

Snyder J, Hong N, McDonald R, Wojtowicz J . A role for adult neurogenesis in spatial long-term memory. Neuroscience. 2005; 130(4):843-52. DOI: 10.1016/j.neuroscience.2004.10.009. View

16.

Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K . Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999; 283(5398):70-4. DOI: 10.1126/science.283.5398.70. View

17.

Winocur G, Martin Wojtowicz J, Sekeres M, Snyder J, Wang S . Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus. 2006; 16(3):296-304. DOI: 10.1002/hipo.20163. View

18.

Rakic S, Zecevic N . Programmed cell death in the developing human telencephalon. Eur J Neurosci. 2000; 12(8):2721-34. DOI: 10.1046/j.1460-9568.2000.00153.x. View

19.

Thornberry N, Lazebnik Y . Caspases: enemies within. Science. 1998; 281(5381):1312-6. DOI: 10.1126/science.281.5381.1312. View

20.

Yu D, Jiang Y, Gao J, Liu B, Chen P . Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats. Neurosci Lett. 2013; 534:41-6. DOI: 10.1016/j.neulet.2012.12.033. View