Neurotoxicity of general anesthetics: An update

Current Pharmaceutical Design

Volumn 18, Issue 38, 2012, Pages 6232-6240

  Vlisides, Phillip ^a   Xie, Zhongcong ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Anesthesia; Beta amyloid protein; Cognitive function; Neurotoxicity

Indexed keywords

AMYLOID BETA PROTEIN; DESFLURANE; ISOFLURANE; NITROUS OXIDE; SEVOFLURANE;

CELL CULTURE; CLINICAL TRIAL; COGNITION; COGNITIVE DEFECT; DRUG INDUCED DISEASE; GENERAL ANESTHESIA; HUMAN; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; REVIEW;

ADOLESCENT; ADULT; AGE FACTORS; AGED; ANESTHESIA, GENERAL; ANESTHETICS, GENERAL; ANIMALS; BRAIN; CHILD; CHILD DEVELOPMENT; CHILD, PRESCHOOL; COGNITION; COGNITION DISORDERS; HUMANS; INFANT; INFANT, NEWBORN; LEARNING; MEMORY; MIDDLE AGED; NEUROTOXICITY SYNDROMES; RISK FACTORS; YOUNG ADULT;

EID: 84873974929     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803832344     Document Type: Review

References (121)

1. Buxton DW. Crawford Williamson Long (1815-1879): the Pioneer of Anaesthesia and the first to suggest and employ Ether Inhalation during Surgical Operations. Proc R Soc Med 1912; 5(Sect Anaesth): 19-45.
2. Crawford W. Long (1815-1878) discoverer of ether for anesthesia. JAMA 1965; 194(9): 1008-9.
3. Heynick F. William T.G. Morton and "The Great Moment". J Hist Dent 2003; 51(1): 27-35.
4. Weiser TG, Regenbogen SE, Thompson KD, et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008; 372(9633): 139-44.
5. Briner A, De Roo M, Dayer A, Muller D, Habre W, Vutskits L. Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology 2010; 112(3): 546-56.
6. Head BP, Patel HH, Niesman IR, Drummond JC, Roth DM, Patel PM. Inhibition of p75 neurotrophin receptor attenuates isofluranemediated neuronal apoptosis in the neonatal central nervous system. Anesthesiology 2009; 110(4): 813-25.
7. Pearn ML, Hu Y, Niesman IR, et al. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology 2012; 116(2): 352-61.
8. Bianchi SL, Tran T, Liu C, et al. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 2008; 29(7): 1002-10.
9. Johnson SA, Young C, Olney JW. Isoflurane-induced neuroapoptosis in the developing brain of nonhypoglycemic mice. J Neurosurg Anesthesiol 2008; 20(1): 21-8.
10. Zhang G, Dong Y, Zhang B, et al. Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. J Neurosci 2008; 28(17): 4551-60.
11. Xie Z, Culley DJ, Dong Y, et al. The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid betaprotein level in vivo. Ann Neurol 2008; 64(6): 618-27.
12. Zhang Y, Zhen Y, Dong Y, et al. Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Abeta oligomerization. PLoS One 2011; 6(11): e27019.
13. Zhang Y, Xu Z, Wang H, et al. Anesthetics isoflurane and desflurane differently affect mitochondrial function and learning and memory. Ann Neurol 2012; 71(5): 687-98.
14. Stratmann G, Sall JW, Bell JS, et al. Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats. Anesthesiology 2010; 112(2): 305-15.
15. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23(3): 876-82.
16. Culley DJ, Baxter MG, Crosby CA, Yukhananov R, Crosby G. Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth Analg 2004; 99(5): 1393-7; table of contents.
17. Stratmann G, Sall JW, May LD, et al. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology 2009; 110(4): 834-48.
18. Olney JW, Brambrink AM, Avidan MS, Farber NB, Back SA. Isoflurane-induced oligoapoptosis in neonatal rhesus macaque brain. Anesthesiology 2010; 112(4): 834-41.
19. Brambrink AM, Evers AS, Avidan MS, et al. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010; 112(4): 834-41.
20. Palanisamy A, Baxter MG, Keel PK, Xie Z, Crosby G, Culley DJ. Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults. Anesthesiology 2011; 114(3): 521-8.
21. Wei H, Liang G, Yang H, et al. The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology 2008; 108(2): 251-60.
22. Wei H, Xie Z. Anesthesia, calcium homeostasis and Alzheimer's disease. Curr Alzheimer Res 2009; 6(1): 30-5.
23. Zhang Y, Dong Y, Wu X, et al. The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem 2010; 285(6): 4025-37.
24. Sall JW, Stratmann G, Leong J, et al. Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture. Anesthesiology 2009; 110(4): 826-33.
25. Tung A, Herrera S, Fornal CA, Jacobs BL. The effect of prolonged anesthesia with isoflurane, propofol, dexmedetomidine, or ketamine on neural cell proliferation in the adult rat. Anesth Analg 2008; 106(6): 1772-7.
26. Culley DJ, Boyd JD, Palanisamy A, et al. Isoflurane decreases selfrenewal capacity of rat cultured neural stem cells. Anesthesiology 2011; 115(4): 754-63.
27. Liang G, Ward C, Peng J, Zhao Y, Huang B, Wei H. Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice. Anesthesiology 2010; 112(6): 1325-34.
28. Eckenhoff RG, Johansson JS, Wei H, et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004; 101(3): 703-9.
29. Xie Z, Dong Y, Maeda U, et al. The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels. Anesthesiology 2006; 104(5): 988-94.
30. Xie Z, Dong Y, Maeda U, et al. Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia. J Gerontol A Biol Sci Med Sci 2006; 61(12): 1300-6.
31. Xie Z, Dong Y, Maeda U, et al. The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci 2007; 27(6): 1247-54.
32. Tanzi RE. The synaptic Abeta hypothesis of Alzheimer disease. Nat Neurosci 2005; 8(8): 977-9.
33. Wu X, Lu Y, Dong Y, et al. The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-alpha, IL-6, and IL-1beta. Neurobiol Aging 2012; 33(7): 1364-78.
34. Bianchi SL, Caltagarone BM, Laferla FM, Eckenhoff RG, Kelz MB. Inhaled anesthetic potency in aged Alzheimer mice. Anesth Analg 2010; 110(2): 427-30.
35. Eckel B, Richtsfeld M, Starker L, Blobner M. Transgenic Alzheimer mice have a larger minimum alveolar anesthetic concentration of isoflurane than their nontransgenic littermates. Anesth Analg 2010; 110(2): 438-41.
36. Istaphanous GK, Howard J, Nan X, et al. Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology 2011; 114(3): 578-87.
37. Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dysfunction 1-2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand 2000; 44(10): 1246-51.
38. Sloan MH, Conard PF, Karsunky PK, Gross JB. Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia. Anesth Analg 1996; 82(3): 528-32.
39. Ranieri R, Martinelli G, Pagani I, et al. Maintenance and recovery characteristics of sevoflurane anaesthesia in adult patients. A multicenter, randomized comparison with isoflurane. Minerva Anestesiol 1998; 64(9 Suppl 3): 11-7.
40. Singh D, Rath GP, Dash HH, Bithal PK. Sevoflurane provides better recovery as compared with isoflurane in children undergoing spinal surgery. J Neurosurg Anesthesiol 2009; 21(3): 202-6.
41. Dong Y, Zhang G, Zhang B, et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases betaamyloid protein levels. Arch Neurol 2009; 66(5): 620-31.
42. Lu Y, Wu X, Dong Y, Xu Z, Zhang Y, Xie Z. Anesthetic sevoflurane causes neurotoxicity differently in neonatal naive and Alzheimer disease transgenic mice. Anesthesiology 2010; 112(6): 1404-16.
43. Zhang X, Xue Z, Sun A. Subclinical concentration of sevoflurane potentiates neuronal apoptosis in the developing C57BL/6 mouse brain. Neurosci Lett 2008; 447(2-3): 109-14.
44. Satomoto M, Satoh Y, Terui K, et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009; 110(3): 628-37.
45. Zhang Y, Dong Y, Zheng H, et al. Sevoflurane inhibits neurogenesis and the wnt-catenin signaling pathway in mouse neural progenitor cells. Curr Mol Med 2012 [Epub ahead of print].
46. Liang G, Wang Q, Li Y, et al. A presenilin-1 mutation renders neurons vulnerable to isoflurane toxicity. Anesth Analg 2008; 106(2): 492-500, table of contents.
47. Yang H, Liang G, Hawkins BJ, Madesh M, Pierwola A, Wei H. Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies. Anesthesiology 2008; 109(2): 243-50.
48. Zhang B, Dong Y, Zhang G, et al. The inhalation anesthetic desflurane induces caspase activation and increases amyloid betaprotein levels under hypoxic conditions. J Biol Chem 2008; 283(18): 11866-75.
49. Zhang Y, Dong Y, Wu X, et al. The mitochondrial pathway of anesthetic isoflurane-induced apoptosis. J Biol Chem 2010; 285(6): 4025-37.
50. Loop T, Dovi-Akue D, Frick M, et al. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology 2005; 102(6): 1147-57.
51. Zhang B, Tian M, Zhen Y, et al. The Effects of Isoflurane and Desflurane on Cognitive Function in Humans. Anesth Analg 2012; 114(20): 410-5.
52. Kodama M, Satoh Y, Otsubo Y, et al. Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory. Anesthesiology 2011; 115(5): 979-91.
53. Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008; 109(4): 707-22.
54. Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW. Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain. Neuroscience 2003; 122(3): 609-16.
55. Zhen Y, Dong Y, Wu X, et al. Nitrous oxide plus isoflurane induces apoptosis and increases beta-amyloid protein levels. Anesthesiology 2009; 111(4): 741-52.
56. Culley DJ, Raghavan SV, Waly M, et al. Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats. Anesth Analg 2007; 105(1): 83-8.
57. Cohen Aubart F, Sedel F, Vicart S, Lyon-Caen O, Fontaine B. [Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency]. Rev Neurol (Paris) 2007; 163(3): 362-4.
58. Wang C, Sadovova N, Fu X, et al. The role of the N-methyl-Daspartate receptor in ketamine-induced apoptosis in rat forebrain culture. Neuroscience 2005; 132(4): 967-77.
59. Young C, Jevtovic-Todorovic V, Qin YQ, 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(2): 189-97.
60. Ikonomidou C, Bosch F, Miksa M, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999; 283(5398): 70-4.
61. Scallet AC, Schmued LC, Slikker W, Jr., et al. Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicol Sci 2004; 81(2): 364-70.
62. Slikker W, Jr., Zou X, Hotchkiss CE, et al. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci 2007; 98(1): 145-58.
63. Paule MG, Li M, Allen RR, et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol 2011; 33(2): 220-30.
64. Brambrink AM, Evers AS, Avidan MS, et al. Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain. Anesthesiology 2012; 116(2): 372-84.
65. Boultadakis A, Pitsikas N. Anesthetic ketamine impairs rats' recall of previous information: the nitric oxide synthase inhibitor N-nitro-L-arginine methylester antagonizes this ketamine-induced recognition memory deficit. Anesthesiology 2011; 114(6): 1345-53.
66. Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg 2008; 106(6): 1712-4.
67. Kahraman S, Zup SL, McCarthy MM, Fiskum G. GABAergic mechanism of propofol toxicity in immature neurons. J Neurosurg Anesthesiol 2008; 20(4): 233-40.
68. Whittington RA, Virag L, Marcouiller F, et al. Propofol directly increases tau phosphorylation. PLoS One 2011; 6(1): e16648.
69. Ikonomidou C, Bittigau P, Ishimaru MJ, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000; 287(5455): 1056-60.
70. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci USA 2002; 99(23): 15089-94.
71. Oppenheim RW. Cell death during development of the nervous system. Annu Rev Neurosci 1991; 14: 453-501.
72. Rakic S, Zecevic N. Programmed cell death in the developing human telencephalon. Eur J Neurosci 2000; 12(8): 2721-34.
73. Rappaport B, Mellon RD, Simone A, Woodcock J. Defining safe use of anesthesia in children. N Engl J Med 2011; 364(15): 1387-90.
74. Belluck P. F.D.A. to Study Whether Anesthesia Poses Cognitive Risks in Young Children. The New York Times 2011; Sect. 1.
75. Durieux M, Davis PJ. The Safety of Key Inhaled and Intravenous Drugs in Pediatrics (SAFEKIDS): an update. Anesth Analg 2010; 110(5): 1265-7.
76. Olney JW, Wozniak DF, Jevtovic-Todorovic V, Farber NB, Bittigau P, Ikonomidou C. Drug-induced apoptotic neurodegeneration in the developing brain. Brain Pathol 2002; 12(4): 488-98.
77. Jevtovic-Todorovic V, Benshoff N, Olney JW. Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats. Br J Pharmacol 2000; 130(7): 1692-8.
78. Olney JW, Young C, Wozniak DF, Jevtovic-Todorovic V, Ikonomidou C. Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol Sci 2004; 25(3): 135-9.
79. Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110(4): 796-804.
80. Arnold JH, Truog RD, Rice SA. Prolonged administration of isoflurane to pediatric patients during mechanical ventilation. Anesth Analg 1993; 76(3): 520-6.
81. Kelsall AW, Ross-Russell R, Herrick MJ. Reversible neurologic dysfunction following isoflurane sedation in pediatric intensive care. Crit Care Med 1994; 22(6): 1032-4.
82. Kalkman CJ, Peelen L, Moons KG, et al. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology 2009; 110(4): 805-12.
83. DiMaggio C, Sun LS, Li G. Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort. Anesth Analg 2011; 113(5): 1143-51.
84. Flick RP, Lee K, Hofer RE, et al. Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities. Anesth Analg 2011; 112(6): 1424-31.
85. Bartels M, Althoff RR, Boomsma DI. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res Hum Genet 2009; 12(3): 246-53.
86. Sun L. Early childhood general anaesthesia exposure and neurocognitive development. Br J Anaesth 2010; 105 Suppl 1: i61-8.
87. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998; 351(9106): 857-61.
88. Leung JM, Sands LP. Long-term cognitive decline: is there a link to surgery and anesthesia? Anesthesiology 2009; 111(5): 931-2.
89. Rudolph JL, Schreiber KA, Culley DJ, et al. Measurement of postoperative cognitive dysfunction after cardiac surgery: a systematic review. Acta Anaesthesiol Scand 2010; 54(6): 663-77.
90. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008; 108(1): 18-30.
91. Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. J Neurosci 2007; 27(12): 3090-7.
92. Planel E, Krishnamurthy P, Miyasaka T, et al. Anesthesia-induced hyperphosphorylation detaches 3-repeat tau from microtubules without affecting their stability in vivo. J Neurosci 2008; 28(48): 12798-807.
93. Planel E, Bretteville A, Liu L, et al. Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEB J 2009; 23(8): 2595-604.
94. Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 2000; 33(1): 95-130.
95. Newman S, Stygall J, Hirani S, Shaefi S, Maze M. Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. Anesthesiology 2007; 106(3): 572-90.
96. Rasmussen LS, Johnson T, Kuipers HM, et al. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. [Clinical Trial, Comparative Study, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't] 2003; 47(3): 260-6.
97. Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology 2009; 111(5): 964-70.
98. Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg 2011; 112(5): 1179-85.
99. McDonagh DL, Mathew JP, White WD, et al. Cognitive function after major noncardiac surgery, apolipoprotein E4 genotype, and biomarkers of brain injury. Anesthesiology 2010; 112(4): 852-9.
100. Rasmussen LS, Schmehl W, Jakobsson J. Comparison of xenon with propofol for supplementary general anaesthesia for knee replacement: a randomized study. Br J Anaesth 2006; 97(2): 154-9.
101. Coburn M, Baumert JH, Roertgen D, et al. Emergence and early cognitive function in the elderly after xenon or desflurane anaesthesia: a double-blinded randomized controlled trial. Br J Anaesth 2007; 98(6): 756-62.
102. Hocker J, Stapelfeldt C, Leiendecker J, et al. Postoperative neurocognitive dysfunction in elderly patients after xenon versus propofol anesthesia for major noncardiac surgery: a double-blinded randomized controlled pilot study. Anesthesiology 2009; 110(5): 1068-76.
103. Rortgen D, Kloos J, Fries M, et al. Comparison of early cognitive function and recovery after desflurane or sevoflurane anaesthesia in the elderly: a double-blinded randomized controlled trial. Br J Anaesth 2010; 104(2): 167-74.
104. Kitano H, Kirsch JR, Hurn PD, Murphy SJ. Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain. J Cereb Blood Flow Metab 2007; 27(6): 1108-28.
105. Loepke AW, Priestley MA, Schultz SE, McCann J, Golden J, Kurth CD. Desflurane improves neurologic outcome after low-flow cardiopulmonary bypass in newborn pigs. Anesthesiology 2002; 97(6): 1521-7.
106. Kurth CD, Priestley M, Watzman HM, McCann J, Golden J. Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs. Anesthesiology 2001; 95(4): 959-64.
107. Sakai H, Sheng H, Yates RB, Ishida K, Pearlstein RD, Warner DS. Isoflurane provides long-term protection against focal cerebral ischemia in the rat. Anesthesiology 2007; 106(1): 92-9; discussion 8-10.
108. Zhou Y, Lekic T, Fathali N, et al. Isoflurane posttreatment reduces neonatal hypoxic-ischemic brain injury in rats by the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway. Stroke 2010; 41(7): 1521-7.
109. Michenfelder JD, Sundt TM, Fode N, Sharbrough FW. Isoflurane when compared to enflurane and halothane decreases the frequency of cerebral ischemia during carotid endarterectomy. Anesthesiology 1987; 67(3): 336-40.
110. Bellinger DC, Wypij D, Kuban KC, et al. Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Circulation 1999; 100(5): 526-32.
111. Bellinger DC, Jonas RA, Rappaport LA, et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995; 332(9): 549-55.
112. Limperopoulos C, Majnemer A, Shevell MI, et al. Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. J Pediatr 2002; 141(1): 51-8.
113. Miller G, Eggli KD, Contant C, Baylen BG, Myers JL. Postoperative neurologic complications after open heart surgery on young infants. Arch Pediatr Adolesc Med 1995; 149(7): 764-8.
114. Bickler PE, Buck LT, Hansen BM. Effects of isoflurane and hypothermia on glutamate receptor-mediated calcium influx in brain slices. Anesthesiology 1994; 81(6): 1461-9.
115. Kudo M, Aono M, Lee Y, Massey G, Pearlstein RD, Warner DS. Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures. Anesthesiology 2001; 95(3): 756-65.
116. Liu Y, Xiong L, Chen S, Wang Q. Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists. Can J Anaesth 2006; 53(2): 194-201.
117. Kapinya KJ, Lowl D, Futterer C, et al. Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent. Stroke 2002; 33(7): 1889-98.
118. Kapinya KJ, Prass K, Dirnagl U. Isoflurane induced prolonged protection against cerebral ischemia in mice: a redox sensitive mechanism? Neuroreport 2002; 13(11): 1431-5.
119. Blanck TJ, Haile M, Xu F, et al. Isoflurane pretreatment ameliorates postischemic neurologic dysfunction and preserves hippocampal Ca2+/calmodulin-dependent protein kinase in a canine cardiac arrest model. Anesthesiology 2000; 93(5): 1285-93.
120. Pan C, Xu Z, Dong Y, et al. The potential dual effects of anesthetic isoflurane on hypoxia-induced caspase-3 activation and increases in beta-site amyloid precursor protein-cleaving enzyme levels. Anesth Analg 2011; 113(1): 145-52.
121. Zhang J, Zhou W, Qiao H. Bioenergetic homeostasis decides neuroprotection or neurotoxicity induced by volatile anesthetics: a uniform mechanism of dual effects. Med Hypotheses 2011; 77(2): 223-9.