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. 2007 Aug 9;13(3):333–351. doi: 10.1111/j.1527-3458.2007.00015.x

Neuroprotective Effects of Propofol in Acute Cerebral Injury

Chiara Adembri 1, Luna Venturi 1, Domenico E Pellegrini‐Giampietro 2
PMCID: PMC6494151  PMID: 17894649

ABSTRACT

Propofol (2,6‐diisopropylphenol) is one of the most popular agents used for induction of anesthesia and long‐term sedation, owing to its favorable pharmacokinetic profile, which ensures a rapid recovery even after prolonged administration. A neuroprotective effect, beyond that related to the decrease in cerebral metabolic rate for oxygen, has been shown to be present in many in vitro and in vivo established experimental models of mild/moderate acute cerebral ischemia. Experimental studies on traumatic brain injury are limited and less encouraging. Despite the experimental results and the positive effects on cerebral physiology (propofol reduces cerebral blood flow but maintains coupling with cerebral metabolic rate for oxygen and decreases intracranial pressure, allowing optimal intraoperative conditions during neurosurgical operations), no clinical study has yet indicated that propofol may be superior to other anesthetics in improving the neurological outcome following acute cerebral injury. Therefore, propofol cannot be indicated as an established clinical neuroprotectant per se, but it might play an important role in the so‐called multimodal neuroprotection, a global strategy for the treatment of acute injury of the brain that includes preservation of cerebral perfusion, temperature control, prevention of infections, and tight glycemic control.

Keywords: Cerebral ischemia, Neurodegeneration, Neuroprotection, Neuroresuscitation, Propofol, Traumatic brain injury

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The authors have no conflict of interest.

REFERENCES

  1. Acquaviva R, Campisi A, Murabito P, Raciti G, Avola R, Mangiameli S, Musumeci I, Barcellona ML, Vanella A, Li VG (2004) Propofol attenuates peroxynitrite‐mediated DNA damage and apoptosis in cultured astrocytes: An alternative protective mechanism. Anesthesiology 101:1363–1371. [DOI] [PubMed] [Google Scholar]
  2. Adembri C, Venturi L, Tani A, Chiarugi A, Gramigni E, Cozzi A, Pancani T, De Gaudio RA, Pellegrini‐Giampietro DE (2006) Neuroprotective effects of propofol in models of cerebral ischemia: Inhibition of mitochondrial swelling as a possible mechanism. Anesthesiology 104:80–89. [DOI] [PubMed] [Google Scholar]
  3. Amorim P, Chambers G, Cottrell J, Kass IS (1995) Propofol reduces neuronal transmission damage and attenuates the changes in calcium, potassium, and sodium during hyperthermic anoxia in the rat hippocampal slice. Anesthesiology 83:1254–1265. [DOI] [PubMed] [Google Scholar]
  4. Arcadi FA, Rapisarda A, De Luca R, Trimarchi GR, Costa G (1996) Effect of 2,6‐diisopropylphenol on the delayed hippocampal cell loss following transient forebrain ischemia in the gerbil. Life Sci 58:961–970. [DOI] [PubMed] [Google Scholar]
  5. Baker MT, Naguib M (2005) Propofol: The challenges of formulation. Anesthesiology 103:860–876. [DOI] [PubMed] [Google Scholar]
  6. Bayona NA, Gelb AW, Jiang Z, Wilson JX, Urquhart BL, Cechetto DF (2004) Propofol neuroprotection in cerebral ischemia and its effects on low‐molecular‐weight antioxidants and skilled motor tasks. Anesthesiology 100:1151–1159. [DOI] [PubMed] [Google Scholar]
  7. Bhardwaj A, Castro III AF, Alkayed NJ, Hurn PD, Kirsch JR (2001) Anesthetic choice of halothane versus propofol: Impact on experimental perioperative stroke. Stroke 32:1920–1925. [DOI] [PubMed] [Google Scholar]
  8. Bickler PE, Buck LT, Feiner JR (1995) Volatile and intravenous anesthetics decrease glutamate release from cortical brain slices during anoxia. Anesthesiology 83:1233–1240. [DOI] [PubMed] [Google Scholar]
  9. Boisseau N, Madany M, Staccini P, Armando G, Martin F, Grimaud D, Raucoules‐Aime M (2002) Comparison of the effects of sevoflurane and propofol on cortical somatosensory evoked potentials. Br J Anaesth 88:785–789. [DOI] [PubMed] [Google Scholar]
  10. Borgeat A, Wilder‐Smith OH, Saiah M, Rifat K (1992) Subhypnotic doses of propofol relieve pruritus induced by epidural and intrathecal morphine. Anesthesiology 76:510–512. [DOI] [PubMed] [Google Scholar]
  11. Borgeat A, Wilder‐Smith O, Forni M, Suter PM (1994) Adjuvant propofol enables better control of nausea and emesis secondary to chemotherapy for breast cancer. Can J Anaesth 41:1117–1119. [DOI] [PubMed] [Google Scholar]
  12. Briggs LP, Clarke RS, Watkins J (1982) An adverse reaction to the administration of disoprofol (Diprivan). Anaesthesia 37:1099–1101. [DOI] [PubMed] [Google Scholar]
  13. Bryson HM, Fulton BR, Faulds D (1995) Propofol. An update of its use in anaesthesia and conscious sedation. Drugs 50:513–559. [DOI] [PubMed] [Google Scholar]
  14. Buggy DJ, Nicol B, Rowbotham DJ, Lambert DG (2000) Effects of intravenous anesthetic agents on glutamate release: A role for GABAA receptor‐mediated inhibition. Anesthesiology 92:1067–1073. [DOI] [PubMed] [Google Scholar]
  15. Cenic A, Craen RA, Lee TY, Gelb AW (2002) Cerebral blood volume and blood flow responses to hyperventilation in brain tumors during isoflurane or propofol anesthesia. Anesth Analg 94:661–666. [DOI] [PubMed] [Google Scholar]
  16. Chieregato A, Calzolari F, Trasforini G, Targa L, Latronico N (2003) Normal jugular bulb oxygen saturation. J Neurol Neurosurg Psychiatry 74:784–786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Concas A, Santoro G, Serra M, Sanna E, Biggio G (1991) Neurochemical action of the general anaesthetic propofol on the chloride ion channel coupled with GABAA receptors. Brain Res 542:225–232. [DOI] [PubMed] [Google Scholar]
  18. Cook DJ, Oliver WC, Jr ., Orszulak TA, Daly RC (1994) A prospective, randomized comparison of cerebral venous oxygen saturation during normothermic and hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 107:1020–1028. [PubMed] [Google Scholar]
  19. Daskalopoulos R, Korcok J, Farhangkhgoee P, Karmazyn M, Gelb AW, Wilson JX (2001) Propofol protection of sodium‐hydrogen exchange activity sustains glutamate uptake during oxidative stress. Anesth Analg 93:1199–1204. [DOI] [PubMed] [Google Scholar]
  20. De Keyser J, Sulter G, Luiten PG (1999) Clinical trials with neuroprotective drugs in acute ischaemic stroke: Are we doing the right thing? Trends Neurosci 22:535–540. [DOI] [PubMed] [Google Scholar]
  21. Eberspacher E, Heimann K, Hollweck R, Werner C, Schneider G, Engelhard K (2006) The effect of electroencephalogram‐targeted high‐ and low‐dose propofol infusion on histopathological damage after traumatic brain injury in the rat. Anesth Analg 103:1527–1533. [DOI] [PubMed] [Google Scholar]
  22. Engelhard K, Werner C, Eberspacher E, Pape M, Stegemann U, Kellermann K, Hollweck R, Hutzler P, Kochs E (2004) Influence of propofol on neuronal damage and apoptotic factors after incomplete cerebral ischemia and reperfusion in rats: A long‐term observation. Anesthesiology 101:912–917. [DOI] [PubMed] [Google Scholar]
  23. Engelhard K, Werner C, Hoffman WE, Matthes B, Blobner M, Kochs E (2003) The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats. Anesth Analg 97:1155–1161. [DOI] [PubMed] [Google Scholar]
  24. Ergun R, Akdemir G, Sen S, Tasci A, Ergungor F (2002) Neuroprotective effects of propofol following global cerebral ischemia in rats. Neurosurg Rev 25:95–98. [DOI] [PubMed] [Google Scholar]
  25. Feiner JR, Bickler PE, Estrada S, Donohoe PH, Fahlman CS, Schuyler JA (2005) Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures. Anesth Analg 100:215–225. [DOI] [PubMed] [Google Scholar]
  26. Fox J, Gelb AW, Enns J, Murkin JM, Farrar JK, Manninen PH (1992) The responsiveness of cerebral blood flow to changes in arterial carbon dioxide is maintained during propofol‐nitrous oxide anesthesia in humans. Anesthesiology 77:453–456. [DOI] [PubMed] [Google Scholar]
  27. Fulton B, Sorkin EM (1995) Propofol: An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation. Drugs 50:636–657. [DOI] [PubMed] [Google Scholar]
  28. Gelb AW, Bayona NA, Wilson JX, Cechetto DF (2002) Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 96:1183–1190. [DOI] [PubMed] [Google Scholar]
  29. Gupta A, Stierer T, Zuckerman R, Sakima N, Parker SD, Fleisher LA (2004) Comparison of recovery profile after ambulatory anesthesia with propofol, isoflurane, sevoflurane and desflurane: A systematic review. Anesth Analg 98:632–641. [DOI] [PubMed] [Google Scholar]
  30. Hans P, Bonhomme V (2006) Why we still use intravenous drugs as the basic regimen for neurosurgical anaesthesia. Curr Opin Anaesthesiol 19:498–503. [DOI] [PubMed] [Google Scholar]
  31. Hans P, Bonhomme V, Collette J, Albert A, Moonen G (1994) Propofol protects cultured rat hippocampal neurons against N‐methyl‐D‐aspartate receptor‐mediated glutamate toxicity. J Neurosurg Anesthesiol 6:249–253. [DOI] [PubMed] [Google Scholar]
  32. Hollrigel GS, Toth K, Soltesz I (1996) Neuroprotection by propofol in acute mechanical injury: Role of GABAergic inhibition. J Neurophysiol 76:2412–2422. [DOI] [PubMed] [Google Scholar]
  33. Iijima T, Mishima T, Akagawa K, Iwao Y (2006) Neuroprotective effect of propofol on necrosis and apoptosis following oxygen‐glucose deprivation: Relationship between mitochondrial membrane potential and mode of death. Brain Res 1099:25–32. [DOI] [PubMed] [Google Scholar]
  34. Ishii H, Arai T, Segawa H, Morikawa S, Inubushi T, Fukuda K (2002) Effects of propofol on lactate accumulation and oedema formation in focal cerebral ischaemia in hyperglycaemic rats. Br J Anaesth 88:412–417. [DOI] [PubMed] [Google Scholar]
  35. Ito H, Watanabe Y, Isshiki A, Uchino H (1999) Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 43:153–162. [DOI] [PubMed] [Google Scholar]
  36. James R, Glen JB (1980) Synthesis, biological evaluation, and preliminary structure‐activity considerations of a series of alkylphenols as intravenous anesthetic agents. J Med Chem 23:1350–1357. [DOI] [PubMed] [Google Scholar]
  37. Kadoi Y, Saito S, Kunimoto F, Goto F, Fujita N (2003) Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction. Ann Thorac Surg 75:840–846. [DOI] [PubMed] [Google Scholar]
  38. Kaisti KK, Metsahonkala L, Teras M, Oikonen V, Aalto S, Jaaskelainen S, Hinkka S, Scheinin H (2002) Effects of surgical levels of propofol and sevoflurane anesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiology 96:1358–1370. [DOI] [PubMed] [Google Scholar]
  39. Kanbak M, Saricaoglu F, Avci A, Ocal T, Koray Z, Aypar U (2004) Propofol offers no advantage over isoflurane anesthesia for cerebral protection during cardiopulmonary bypass: A preliminary study of S‐100beta protein levels. Can J Anaesth 51:712–717. [DOI] [PubMed] [Google Scholar]
  40. Kanto J, Gepts E (1989) Pharmacokinetic implications for the clinical use of propofol. Clin Pharmacokinet 17:308–326. [DOI] [PubMed] [Google Scholar]
  41. Kaptanoglu E, Sen S, Beskonakli E, Surucu HS, Tuncel M, Kilinc K, Taskin Y (2002) Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury. J Neurosurg Anesthesiol 14:114–122. [DOI] [PubMed] [Google Scholar]
  42. Kawaguchi M, Furuya H, Patel PM (2005) Neuroprotective effects of anesthetic agents. J Anesth 19:150–156. [DOI] [PubMed] [Google Scholar]
  43. Kay B, Rolly G (1977) I.C.I. 35868, a new intravenous induction agent. Acta Anaesthesiol Belg 28:303–316. [PubMed] [Google Scholar]
  44. Khaja AM, Grotta JC (2007) Established treatments for acute ischaemic stroke. Lancet 369:319–330. [DOI] [PubMed] [Google Scholar]
  45. Kochs E, Hoffman WE, Werner C, Thomas C, Albrecht RF, Schulte am Esch J (1992) The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology 76:245–252. [DOI] [PubMed] [Google Scholar]
  46. Koerner IP, Brambrink AM (2006) Brain protection by anesthetic agents. Curr Opin Anaesthesiol 19:481–486. [DOI] [PubMed] [Google Scholar]
  47. Lingamaneni R, Birch ML, Hemmings HC, Jr . (2001) Widespread inhibition of sodium channel‐dependent glutamate release from isolated nerve terminals by isoflurane and propofol. Anesthesiology 95:1460–1466. [DOI] [PubMed] [Google Scholar]
  48. Liu LL, Gropper MA (2003) Postoperative analgesia and sedation in the adult intensive care unit: A guide to drug selection. Drugs 63:755–767. [DOI] [PubMed] [Google Scholar]
  49. Ludbrook GL, Visco E, Lam AM (2002) Propofol: Relation between brain concentrations, electroencephalogram, middle cerebral artery blood flow velocity, and cerebral oxygen extraction during induction of anesthesia. Anesthesiology 97:1363–1370. [DOI] [PubMed] [Google Scholar]
  50. Magni G, Baisi F, La RI, Imperiale C, Fabbrini V, Pennacchiotti ML, Rosa G (2005) No difference in emergence time and early cognitive function between sevoflurane‐fentanyl and propofol‐remifentanyl in patients undergoing craniotomy for supratentorial intracranial surgery. J Neurosurg Anesthesiol 17:134–138. [DOI] [PubMed] [Google Scholar]
  51. Mattson MP, Kroemer G (2003) Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol Med 9:196–205. [DOI] [PubMed] [Google Scholar]
  52. Michenfelder JD, Theye RA (1973) Cerebral protection by thiopental during hypoxia. Anesthesiology 39:510‐517. [DOI] [PubMed] [Google Scholar]
  53. Mortero RF, Clark LD, Tolan MM, Metz RJ, Tsueda K, Sheppard RA (2001) The effects of small‐dose ketamine on propofol sedation: Respiration, postoperative mood, perception, cognition, and pain. Anesth Analg 92:1465–1469. [DOI] [PubMed] [Google Scholar]
  54. Munoz HR, Nunez GE, De La Fuente JE, Campos MG (2002) The effect of nitrous oxide on jugular bulb oxygen saturation during remifentanyl plus target‐controlled infusion propofol or sevoflurane in patients with brain tumors. Anesth Analg 94:389–392, table. [DOI] [PubMed] [Google Scholar]
  55. Nandate K, Vuylsteke A, Ratsep I, Messahel S, Oduro‐Dominah A, Menon DK, Matta BF (2000) Effects of isoflurane, sevoflurane and propofol anaesthesia on jugular venous oxygen saturation in patients undergoing coronary artery bypass surgery. Br J Anaesth 84:631–633. [DOI] [PubMed] [Google Scholar]
  56. Newman MF, Murkin JM, Roach G, Croughwell ND, White WD, Clements FM, Reves JG (1995) Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. CNS Subgroup of McSPI. Anesth Analg 81:452–457. [DOI] [PubMed] [Google Scholar]
  57. Newman S, Stygall J, Hirani S, Shaefi S, Maze M (2007) Postoperative cognitive dysfunction after noncardiac surgery: A systematic review. Anesthesiology 106:572–590. [DOI] [PubMed] [Google Scholar]
  58. Nicol B, Rowbotham DJ, Lambert DG (1995) Glutamate uptake is not a major target site for anaesthetic agents. Br J Anaesth 75:61–65. [DOI] [PubMed] [Google Scholar]
  59. Orser BA, Wang LY, Pennefather PS, MacDonald JF (1994) Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci 14:7747–7760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Orser BA, Bertlik M, Wang LY, MacDonald JF (1995) Inhibition by propofol (2,6 di‐isopropylphenol) of the N‐methyl‐D‐aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br J Pharmacol 116:1761–1768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Ozturk E, Demirbilek S, Kadir BA, Saricicek V, Gulec M, Akyol O, Ozcan EM (2005) Antioxidant properties of propofol and erythropoietin after closed head injury in rats. Prog Neuropsychopharmacol Biol Psychiat 29:922–927. [DOI] [PubMed] [Google Scholar]
  62. Patel P (2004) No magic bullets: the ephemeral nature of anesthetic‐mediated neuroprotection. Anesthesiology 100:1049–1051. [DOI] [PubMed] [Google Scholar]
  63. Patel S, Wohlfeil ER, Rademacher DJ, Carrier EJ, Perry LJ, Kundu A, Falck JR, Nithipatikom K, Campbell WB, Hillard CJ (2003) The general anesthetic propofol increases brain N‐arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol 139:1005–1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Peters CE, Korcok J, Gelb AW, Wilson JX (2001) Anesthetic concentrations of propofol protect against oxidative stress in primary astrocyte cultures: Comparison with hypothermia. Anesthesiology 94:313–321. [DOI] [PubMed] [Google Scholar]
  65. Petersen KD, Landsfeldt U, Cold GE, Petersen CB, Mau S, Hauerberg J, Holst P, Olsen KS (2003) Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: A randomized prospective study of patients subjected to craniotomy in propofol‐fentanyl, isoflurane‐fentanyl, or sevoflurane‐fentanyl anesthesia. Anesthesiology 98:329–336. [DOI] [PubMed] [Google Scholar]
  66. Pittman JE, Sheng H, Pearlstein R, Brinkhous A, Dexter F, Warner DS (1997) Comparison of the effects of propofol and pentobarbital on neurologic outcome and cerebral infarct size after temporary focal ischemia in the rat. Anesthesiology 87:1139–1144. [DOI] [PubMed] [Google Scholar]
  67. Preckel B, Weber NC, Sanders RD, Maze M, Schlack W (2006) Molecular mechanisms transducing the anesthetic, analgesic, and organ‐protective actions of xenon. Anesthesiology 105:187–197. [DOI] [PubMed] [Google Scholar]
  68. Qi S, Zhan RZ, Wu C, Fujihara H, Taga K, Shimoji K (2002) The effects of thiopental and propofol on cell swelling induced by oxygen/glucose deprivation in the CA1 pyramidal cell layer of rat hippocampal slices. Anesth Analg 94:655–660. [DOI] [PubMed] [Google Scholar]
  69. Rasmussen M, Ostergaard L, Juul N, Gyldensted C, Poulsen PV, Cold GE (2004) Do indomethacin and propofol cause cerebral ischemic damage? Diffusion‐weighted magnetic resonance imaging in patients undergoing craniotomy for brain tumors. Anesthesiology 101:872–878. [DOI] [PubMed] [Google Scholar]
  70. Ratnakumari L, Hemmings HC, Jr (1997) Effects of propofol on sodium channel‐dependent sodium influx and glutamate release in rat cerebrocortical synaptosomes. Anesthesiology 86:428–439. [DOI] [PubMed] [Google Scholar]
  71. Ridenour TR, Warner DS, Todd MM, Gionet TX (1992) Comparative effects of propofol and halothane on outcome from temporary middle cerebral artery occlusion in the rat. Anesthesiology 76:807–812. [DOI] [PubMed] [Google Scholar]
  72. Schelling G, Hauer D, Azad SC, Schmoelz M, Chouker A, Schmidt M, Hornuss C, Rippberger M, Briegel J, Thiel M, et al (2006) Effects of general anesthesia on anandamide blood levels in humans. Anesthesiology 104:273–277. [DOI] [PubMed] [Google Scholar]
  73. Shibuta S, Sriranganathan V, Inoue T, Shimizu T, Tomi K, Mashimo T (2001) The effects of propofol on NMDA‐ or nitric oxide‐mediated neurotoxicity in vitro. NeuroReport 12:295–298. [DOI] [PubMed] [Google Scholar]
  74. Sitar SM, Hanifi‐Moghaddam P, Gelb A, Cechetto DF, Siushansian R, Wilson JX (1999) Propofol prevents peroxide‐induced inhibition of glutamate transport in cultured astrocytes. Anesthesiology 90:1446–1453. [DOI] [PubMed] [Google Scholar]
  75. Souter MJ, Andrews PJ, Alston RP (1998) Propofol does not ameliorate cerebral venous oxyhemoglobin desaturation during hypothermic cardiopulmonary bypass. Anesth Analg 86:926–931. [DOI] [PubMed] [Google Scholar]
  76. Statler KD, Alexander H, Vagni V, Dixon CE, Clark RS, Jenkins L, Kochanek PM (2006) Comparison of seven anesthetic agents on outcome after experimental traumatic brain injury in adult, male rats. J Neurotrauma 23:97–108. [DOI] [PubMed] [Google Scholar]
  77. Stocchetti N (2005) Brain and sepsis: Functional impairment, structural damage, and markers. Anesth Analg 101:1463–1464. [DOI] [PubMed] [Google Scholar]
  78. Todd MM, Warner DS (1992) A comfortable hypothesis reevaluated. Cerebral metabolic depression and brain protection during ischemia. Anesthesiology 76:161–164. [PubMed] [Google Scholar]
  79. Tsai YC, Huang SJ, Lai YY, Chang CL, Cheng JT (1994) Propofol does not reduce infarct volume in rats undergoing permanent middle cerebral artery occlusion. Acta Anaesthesiol Sin 32:99–104. [PubMed] [Google Scholar]
  80. Van Der Stelt M, Di Marzo, V (2005) Cannabinoid receptors and their role in neuroprotection. Neuromol Med 7:37–50. [DOI] [PubMed] [Google Scholar]
  81. Velly LJ, Guillet BA, Masmejean FM, Nieoullon AL, Bruder NJ, Gouin FM, Pisano PM (2003) Neuroprotective effects of propofol in a model of ischemic cortical cell cultures: Role of glutamate and its transporters. Anesthesiology 99:368–375. [DOI] [PubMed] [Google Scholar]
  82. Wakasugi M, Hirota K, Roth SH, Ito Y (1999) The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. Anesth Analg 88:676–680. [DOI] [PubMed] [Google Scholar]
  83. Walder B, Tramer MR, Seeck M (2002) Seizure‐like phenomena and propofol: A systematic review. Neurology 58:1327–1332. [DOI] [PubMed] [Google Scholar]
  84. Wang J, Yang X, Camporesi CV, Yang Z, Bosco G, Chen C, Camporesi EM (2002) Propofol reduces infarct size and striatal dopamine accumulation following transient middle cerebral artery occlusion: A microdialysis study. Eur J Pharmacol 452:303–308. [DOI] [PubMed] [Google Scholar]
  85. Warner DS (2004) Perioperative neuroprotection: are we asking the right questions? Anesth Analg 98:563–565. [DOI] [PubMed] [Google Scholar]
  86. Weir DL, Goodchild CS, Graham DI (1989) Propofol: effects on indices of cerebral ischemia. J Neurosurg Anesthesiol 1:284–289. [PubMed] [Google Scholar]
  87. Wells BA, Keats AS, Cooley DA (1963) Increased tolerance to cerebral ischemia produced by general anesthesia during temporary carotid occlusion. Surgery 54:216–223. [PubMed] [Google Scholar]
  88. Williams DB, Akabas MH (2002) Structural evidence that propofol stabilizes different GABAA receptor states at potentiating and activating concentrations. J Neurosci 22:7417–7424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Wilson JX, Gelb AW (2002) Free radicals, antioxidants, and neurologic injury: Possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol 14:66–79. [DOI] [PubMed] [Google Scholar]
  90. Wysowski DK, Pollock ML (2006) Reports of death with use of propofol (Diprivan) for nonprocedural (long‐term) sedation and literature review. Anesthesiology 105:1047–1051. [DOI] [PubMed] [Google Scholar]
  91. Yamaguchi S, Hamaguchi S, Mishio M, Okuda Y, Kitajima T (2000) Propofol prevents lipid peroxidation following transient forebrain ischemia in gerbils. Can J Anaesth 47:1025–1030. [DOI] [PubMed] [Google Scholar]
  92. Yamakura T, Sakimura K, Shimoji K, Mishina M (1995) Effects of propofol on various AMPA‐, kainate‐ and NMDA‐selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci Lett 188:187–190. [DOI] [PubMed] [Google Scholar]
  93. Yano T, Nakayama R, Ushijima K (2000) Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: Extracellular glutamate level is not a major determinant. Brain Res 883:69–76. [DOI] [PubMed] [Google Scholar]
  94. Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG (1997) Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol 14:320–326. [DOI] [PubMed] [Google Scholar]
  95. Zhan RZ, Qi S, Wu C, Fujihara H, Taga K, Shimoji K (2001) Intravenous anesthetics differentially reduce neurotransmission damage caused by oxygen‐glucose deprivation in rat hippocampal slices in correlation with N‐methyl‐D‐aspartate receptor inhibition. Crit Care Med 29:808–813. [DOI] [PubMed] [Google Scholar]
  96. Zhu H, Cottrell JE, Kass IS (1997) The effect of thiopental and propofol on NMDA‐ and AMPA‐mediated glutamate excitotoxicity. Anesthesiology 87:944–951. [DOI] [PubMed] [Google Scholar]

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