Advertisement

Translational Stroke Research

, Volume 7, Issue 5, pp 358–367 | Cite as

Anesthesia in Experimental Stroke Research

  • Ulrike Hoffmann
  • Huaxin Sheng
  • Cenk Ayata
  • David S. WarnerEmail author
Original Article

Abstract

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet, their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have species-, drug-, and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both preconditioning and postconditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke.

Keywords

Anesthesia Anesthetic Brain Ischemia Stroke 

Notes

Compliance with Ethical Standards

Supported in part by the National Institutes of Health (1R21NS087157–02).

Conflict of Interest

None.

Ethical Approval

This article does not contain any studies with human participants performed by any of the authors.

Informed Consent

Not applicable.

References

  1. 1.
    Warner DS, James ML, Laskowitz DT, Wijdicks EF. Translational research in acute central nervous system injury: lessons learned and the future. JAMA Neurol. 2014;71(10):1311–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Schifilliti D, Grasso G, Conti A, Fodale V. Anaesthetic-related neuroprotection: intravenous or inhalational agents? CNS Drugs. 2010;24(11):893–907.PubMedGoogle Scholar
  3. 3.
    Kety SS, Schmidt CF. The effects of active and passive hyperventilation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men. J Clin Invest. 1946;25:107–19.PubMedCentralCrossRefGoogle Scholar
  4. 4.
    Himwich WA, Homburger E, et al. Brain metabolism in man; unanesthetized and in pentothal narcosis. Am J Psychiatry. 1947;103(5):689–96.PubMedCrossRefGoogle Scholar
  5. 5.
    Michenfelder JD. The interdependency of cerebral functional and metabolic effects following massive doses of thiopental in the dog. Anesthesiology. 1974;41(3):231–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Michenfelder JD, Theye RA. The effects of anesthesia and hypothermia on canine cerebral ATP and lactate during anoxia produced by decapitation. Anesthesiology. 1970;33(4):430–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Todd MM, Drummond JC. A comparison of the cerebrovascular and metabolic effects of halothane and isoflurane in the cat. Anesthesiology. 1984;60(4):276–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Scheller MS, Tateishi A, Drummond JC, Zornow MH. The effects of sevoflurane on cerebral blood flow, cerebral metabolic rate for oxygen, intracranial pressure, and the electroencephalogram are similar to those of isoflurane in the rabbit. Anesthesiology. 1988;68(4):548–51.PubMedCrossRefGoogle Scholar
  9. 9.
    Van Hemelrijck J, Fitch W, Mattheussen M, Van Aken H, Plets C, Lauwers T. Effect of propofol on cerebral circulation and autoregulation in the baboon. Anesth Analg. 1990;71(1):49–54.PubMedCrossRefGoogle Scholar
  10. 10.
    Nugent M, Artru AA, Michenfelder JD. Cerebral metabolic, vascular and protective effects of midazolam maleate: comparison to diazepam. Anesthesiology. 1982;56(3):172–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Renou AM, Vernhiet J, Macrez P, Constant P, Billerey J, Khadaroo MY, et al. Cerebral blood flow and metabolism during etomidate anaesthesia in man. Br J Anaesth. 1978;50(10):1047–51.PubMedCrossRefGoogle Scholar
  12. 12.
    Post RM, Kennedy C, Shinohara M, Squillace K, Miyaoka M, Suda S, et al. Metabolic and behavioral consequences of lidocaine-kindled seizures. Brain Res. 1984;324(2):295–303.PubMedCrossRefGoogle Scholar
  13. 13.
    Carlsson C, Smith DS, Keykhah MM, Englebach I, Harp JR. The effects of high-dose fentanyl on cerebral circulation and metabolism in rats. Anesthesiology. 1982;57(5):375–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Drummond JC, Dao AV, Roth DM, Cheng CR, Atwater BI, Minokadeh A, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. 2008;108(2):225–32. doi: 10.1097/01.anes.0000299576.00302.4c.PubMedCrossRefGoogle Scholar
  15. 15.
    Vollenweider FX, Leenders KL, Scharfetter C, Antonini A, Maguire P, Missimer J, et al. Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Eur Neuropsychopharmacol. 1997;7(1):9–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Oguchi K, Arakawa K, Nelson SR, Samson F. The influence of droperidol, diazepam, and physostigmine on ketamine-induced behavior and brain regional glucose utilization in rat. Anesthesiology. 1982;57(5):353–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Pelligrino DA, Miletich DJ, Hoffman WE, Albrecht RF. Nitrous oxide markedly increases cerebral cortical metabolic rate and blood flow in the goat. Anesthesiology. 1984;60(5):405–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Dashdorj N, Corrie K, Napolitano A, Petersen E, Mahajan RP, Auer DP. Effects of subanesthetic dose of nitrous oxide on cerebral blood flow and metabolism: a multimodal magnetic resonance imaging study in healthy volunteers. Anesthesiology. 2013;118(3):577–86. doi: 10.1097/ALN.0b013e3182800d58.PubMedCrossRefGoogle Scholar
  19. 19.
    Reinstrup P, Ryding E, Ohlsson T, Sandell A, Erlandsson K, Ljunggren K, et al. Regional cerebral metabolic rate (positron emission tomography) during inhalation of nitrous oxide 50 % in humans. Br J Anaesth. 2008;100(1):66–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Reasoner DK, Warner DS, Todd MM, McAllister A. Effects of nitrous oxide on cerebral metabolic rate in rats anaesthetized with isoflurane. Br J Anaesth. 1990;65(2):210–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Kaisti KK, Langsjo JW, Aalto S, Oikonen V, Sipila H, Teras M, et al. Effects of sevoflurane, propofol, and adjunct nitrous oxide on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology. 2003;99(3):603–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Kofke WA, Garman RH, Tom WC, Rose ME, Hawkins RA. Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain. Anesth Analg. 1992;75(6):953–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Jones MV, Brooks PA, Harrison NL. Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol. 1992;449:279–93.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Yang J, Zorumski CF. Effects of isoflurane on N-methyl-D-aspartate gated ion channels in cultured rat hippocampal neurons. Ann N Y Acad Sci. 1991;625:287–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Irifune M, Sato T, Kamata Y, Nishikawa T, Dohi T, Kawahara M. Evidence for GABA(a) receptor agonistic properties of ketamine: convulsive and anesthetic behavioral models in mice. Anesth Analg. 2000;91(1):230–6.PubMedGoogle Scholar
  26. 26.
    Wakita M, Kotani N, Yamaga T, Akaike N. Nitrous oxide directly inhibits action potential-dependent neurotransmission from single presynaptic boutons adhering to rat hippocampal CA3 neurons. Brain Res Bull. 2015;118:34–45.PubMedCrossRefGoogle Scholar
  27. 27.
    Yamakura T, Mori H, Masaki H, Shimoji K, Mishnina M. Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists. Neuroreport. 1993;4:687–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Mennerick S, Jevtovic-Todorovic V, Todorovic SM, Shen W, Olney JW, Zorumski CF. Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures. J Neurosci. 1998;18(23):9716–26.PubMedGoogle Scholar
  29. 29.
    Dickinson R, Peterson BK, Banks P, Simillis C, Martin JC, Valenzuela CA, et al. Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology. 2007;107(5):756–67.PubMedCrossRefGoogle Scholar
  30. 30.
    Sheng SP, Lei B, James ML, Lascola CD, Venkatraman TN, Jung JY, et al. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology. 2012;117(6):1262–75. doi: 10.1097/ALN.0b013e3182746b81.PubMedCrossRefGoogle Scholar
  31. 31.
    Rex S, Schaefer W, Meyer PH, Rossaint R, Boy C, Setani K, et al. Positron emission tomography study of regional cerebral metabolism during general anesthesia with xenon in humans. Anesthesiology. 2006;105(5):936–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Jensen NF, Todd MM, Kramer DJ, Leonard PA, Warner DS. A comparison of the vasodilating effects of halothane and isoflurane on the isolated rabbit basilar artery with and without intact endothelium. Anesthesiology. 1992;76(4):624–34.PubMedCrossRefGoogle Scholar
  33. 33.
    Gelb AW, Zhang C, Hamilton JT. Propofol induces dilation and inhibits constriction in Guinea pig basilar arteries. Anesth Analg. 1996;83(3):472–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Fukuda S, Murakawa T, Takeshita H, Toda N. Direct effects of ketamine on isolated canine cerebral and mesenteric arteries. Anesth Analg. 1983;62(6):553–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Matta BF, Mayberg TS, Lam AM. Direct cerebrovasodilatory effects of halothane, isoflurane, and desflurane during propofol-induced isoelectric electroencephalogram in humans. Anesthesiology. 1995;83(5):980–5 .discussion 27APubMedCrossRefGoogle Scholar
  36. 36.
    Hansen TD, Warner DS, Todd MM, Vust LJ. Effects of nitrous oxide and volatile anaesthetics on cerebral blood flow. Br J Anaesth. 1989;63(3):290–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Lenz C, Frietsch T, Futterer C, Rebel A, van Ackern K, Kuschinsky W, et al. Local coupling of cerebral blood flow to cerebral glucose metabolism during inhalational anesthesia in rats: desflurane versus isoflurane. Anesthesiology. 1999;91(6):1720–3.PubMedCrossRefGoogle Scholar
  38. 38.
    Franceschini MA, Radhakrishnan H, Thakur K, Wu W, Ruvinskaya S, Carp S, et al. The effect of different anesthetics on neurovascular coupling. NeuroImage. 2010;51(4):1367–77.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Miletich DJ, Ivankovich AD, Albrecht RF, Reimann CR, Rosenberg R, McKissic ED. Absence of autoregulation of cerebral blood flow during halothane and enflurane anesthesia. Anesth Analg. 1976;55(1):100–9.PubMedCrossRefGoogle Scholar
  40. 40.
    McPherson RW, Traystman RJ. Effects of isoflurane on cerebral autoregulation in dogs. Anesthesiology. 1988;69(4):493–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Werner C, Lu H, Engelhard K, Unbehaun N, Kochs E. Sevoflurane impairs cerebral blood flow autoregulation in rats: reversal by nonselective nitric oxide synthase inhibition. Anesth Analg. 2005;101(2):509–16.PubMedCrossRefGoogle Scholar
  42. 42.
    Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology. 1995;83(1):66–76.PubMedCrossRefGoogle Scholar
  43. 43.
    Goettel N, Patet C, Rossi A, Burkhart CS, Czosnyka M, Strebel SP, et al. Monitoring of cerebral blood flow autoregulation in adults undergoing sevoflurane anesthesia: a prospective cohort study of two age groups. J Clin Monit Comput. 2016;30(3):255–64.PubMedCrossRefGoogle Scholar
  44. 44.
    Girling KJ, Cavill G, Mahajan RP. The effects of nitrous oxide and oxygen on transient hyperemic response in human volunteers. Anesth Analg. 1999;89(1):175–80.PubMedGoogle Scholar
  45. 45.
    Steiner LA, Johnston AJ, Chatfield DA, Czosnyka M, Coleman MR, Coles JP, et al. The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients. Anesth Analg. 2003;97(2):572–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Schmidt A, Ryding E, Akeson J. Racemic ketamine does not abolish cerebrovascular autoregulation in the pig. Acta Anaesthesiol Scand. 2003;47(5):569–75.PubMedCrossRefGoogle Scholar
  47. 47.
    Engelhard K, Werner C, Lu H, Mollenberg O, Kochs E. Effect of S-(+)-ketamine on autoregulation of cerebral blood flow. Anasthesiol Intensivmed Notfallmed Schmerzther. 1997;32(12):721–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Engelhard K, Werner C, Mollenberg O, Kochs E. S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans. Can J Anaesth. 2001;48(10):1034–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Ogawa Y, Iwasaki K, Aoki K, Gokan D, Hirose N, Kato J, et al. The different effects of midazolam and propofol sedation on dynamic cerebral autoregulation. Anesth Analg. 2010;111(5):1279–84.PubMedCrossRefGoogle Scholar
  50. 50.
    Ogawa Y, Iwasaki K, Aoki K, Kojima W, Kato J, Ogawa S. Dexmedetomidine weakens dynamic cerebral autoregulation as assessed by transfer function analysis and the thigh cuff method. Anesthesiology. 2008;109(4):642–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Ayad M, Verity MA, Rubinstein EH. Lidocaine delays cortical ischemic depolarization: relationship to electrophysiologic recovery and neuropathology. J Neurosurg Anesthesiol. 1994;6(2):98–110.PubMedCrossRefGoogle Scholar
  52. 52.
    Sasaki R, Hirota K, Roth SH, Yamazaki M. Anoxic depolarization of rat hippocampal slices is prevented by thiopental but not by propofol or isoflurane. Br J Anaesth. 2005;94(4):486–91.PubMedCrossRefGoogle Scholar
  53. 53.
    Nakashima K, Todd MM. Effects of hypothermia, pentobarbital, and isoflurane on postdepolarization amino acid release during complete global cerebral ischemia. Anesthesiology. 1996;85(1):161–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Kobayashi M, Takeda Y, Taninishi H, Takata K, Aoe H, Morita K. Quantitative evaluation of the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia in the gerbil: effects of the anesthetics on ischemic depolarization and extracellular glutamate concentration. J Neurosurg Anesthesiol. 2007;19(3):171–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Verhaegen MJ, Todd MM, Warner DS. A comparison of cerebral ischemic flow thresholds during halothane/N2O and isoflurane/N2O anesthesia in rats. Anesthesiology. 1992;76(5):743–54.PubMedCrossRefGoogle Scholar
  56. 56.
    Wang J, Cottrell JE, Kass IS. Effects of desflurane and propofol on electrophysiological parameters during and recovery after hypoxia in rat hippocampal slice CA1 pyramidal cells. Neuroscience. 2009;160(1):140–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Wang J, Meng F, Cottrell JE, Kass IS. The differential effects of volatile anesthetics on electrophysiological and biochemical changes during and recovery after hypoxia in rat hippocampal slice CA1 pyramidal cells. Neuroscience. 2006;140(3):957–67.PubMedCrossRefGoogle Scholar
  58. 58.
    Verhaegen M, Todd MM, Warner DS. Ischemic depolarization during halothane-nitrous oxide and isoflurane-nitrous oxide anesthesia. An examination of cerebral blood flow threshold and times to depolarization. Anesthesiology. 1994;81(4):965–73.PubMedCrossRefGoogle Scholar
  59. 59.
    Nellgård B, Mackensen GB, Pineda J, Wellons 3rd JC, Pearlstein RD, Warner DS. Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat. Anesthesiology. 2000;93(2):431–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Hartings JA, Shuttleworth CW, Kirov SA, Ayata C, Hinzman JM, Foreman B et al. The continuum of spreading depolarizations in acute cortical lesion development: examining Leao’s legacy. J Cereb Blood Flow Metab. 2016. doi: 10.1177/0271678X16654495.
  61. 61.
    Kudo C, Nozari A, Moskowitz MA, Ayata C. The impact of anesthetics and hyperoxia on cortical spreading depression. Exp Neurol. 2008;212(1):201–6.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Saito R, Graf R, Hubel K, Fujita T, Rosner G, Heiss WD. Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations. J Cereb Blood Flow Metab. 1997;17(8):857–64.PubMedCrossRefGoogle Scholar
  63. 63.
    Takagaki M, Feuerstein D, Kumagai T, Gramer M, Yoshimine T, Graf R. Isoflurane suppresses cortical spreading depolarizations compared to propofol--implications for sedation of neurocritical care patients. Exp Neurol. 2014;252:12–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Zhao L, Nowak Jr TS. Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the spontaneously hypertensive rat: interaction with prior anesthesia and the impact of hyperglycemia. J Cereb Blood Flow Metab. 2015;35(7):1181–90.Google Scholar
  65. 65.
    Kudo C, Toyama M, Boku A, Hanamoto H, Morimoto Y, Sugimura M, et al. Anesthetic effects on susceptibility to cortical spreading depression. Neuropharmacology. 2013;67:32–6.PubMedCrossRefGoogle Scholar
  66. 66.
    Hertle DN, Dreier JP, Woitzik J, Hartings JA, Bullock R, Okonkwo DO, et al. Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury. Brain J Neurol. 2012;135(Pt 8):2390–8.CrossRefGoogle Scholar
  67. 67.
    Sakowitz OW, Kiening KL, Krajewski KL, Sarrafzadeh AS, Fabricius M, Strong AJ, et al. Preliminary evidence that ketamine inhibits spreading depolarizations in acute human brain injury. Stroke. 2009;40(8):e519–22.PubMedCrossRefGoogle Scholar
  68. 68.
    Michenfelder JD, Theye RA. Cerebral protection by thiopental during hypoxia. Anesthesiology. 1973;39(5):510–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Newberg LA, Michenfelder JD. Cerebral protection by isoflurane during hypoxemia or ischemia. Anesthesiology. 1983;59(1):29–35.PubMedCrossRefGoogle Scholar
  70. 70.
    Ishida K, Berger M, Nadler J, Warner DS. Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality. Curr Pharm Des. 2014;20(36):5751–65.PubMedCrossRefGoogle Scholar
  71. 71.
    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.PubMedCrossRefGoogle Scholar
  72. 72.
    Kimbro JR, Kelly PJ, Drummond JC, Cole DJ, Patel PM. Isoflurane and pentobarbital reduce AMPA toxicity in vivo in the rat cerebral cortex. Anesthesiology. 2000;92(3):806–12.PubMedCrossRefGoogle Scholar
  73. 73.
    Harada H, Kelly PJ, Cole DJ, Drummond JC, Patel PM. Isoflurane reduces N-methyl-D-aspartate toxicity in vivo in the rat cerebral cortex. Anesth Analg. 1999;89(6):1442–7.PubMedGoogle Scholar
  74. 74.
    Eilers H, Bickler PE. Hypothermia and isoflurane similarly inhibit glutamate release evoked by chemical anoxia in rat cortical brain slices. Anesthesiology. 1996;85(3):600–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Popovic R, Liniger R, Bickler PE. Anesthetics and mild hypothermia similarly prevent hippocampal neuron death in an in vitro model of cerebral ischemia. Anesthesiology. 2000;92(5):1343–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Elsersy H, Mixco J, Sheng H, Pearlstein RD, Warner DS. Selective gamma-aminobutyric acid type a receptor antagonism reverses isoflurane ischemic neuroprotection. Anesthesiology. 2006;105(1):81–90.PubMedCrossRefGoogle Scholar
  77. 77.
    Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA. Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases. Anesthesiology. 2005;102(3):606–15.PubMedCrossRefGoogle Scholar
  78. 78.
    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 8-10PubMedCrossRefGoogle Scholar
  79. 79.
    Warner DS, McFarlane C, Todd MM, Ludwig P, McAllister AM. Sevoflurane and halothane reduce focal ischemic brain damage in the rat. Possible influence on thermoregulation. Anesthesiology. 1993;79(5):985–92.PubMedCrossRefGoogle Scholar
  80. 80.
    Pape M, Engelhard K, Eberspacher E, Hollweck R, Kellermann K, Zintner S, et al. The long-term effect of sevoflurane on neuronal cell damage and expression of apoptotic factors after cerebral ischemia and reperfusion in rats. Anesth Analg. 2006;103(1):173–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Elsersy H, Sheng H, Lynch JR, Moldovan M, Pearlstein RD, Warner DS. Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat. Anesthesiology. 2004;100(5):1160–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Inoue S, Davis DP, Drummond JC, Cole DJ, Patel PM. The combination of isoflurane and caspase 8 inhibition results in sustained neuroprotection in rats subject to focal cerebral ischemia. Anesth Analg. 2006;102(5):1548–55.PubMedCrossRefGoogle Scholar
  83. 83.
    Jevtovic-Todorovic V, Todorovic S, Mennerick S, Powell K, Dikranian K, Benshoff ND, et al. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature Med. 1998;4:460–3.PubMedCrossRefGoogle Scholar
  84. 84.
    Yokoo N, Sheng H, Mixco J, Homi HM, Pearlstein RD, Warner DS. Intraischemic nitrous oxide alters neither neurologic nor histologic outcome: a comparison with dizocilpine. Anesth Analg. 2004;99(3):896–903.PubMedCrossRefGoogle Scholar
  85. 85.
    David HN, Leveille F, Chazalviel L, MacKenzie ET, Buisson A, Lemaire M, et al. Reduction of ischemic brain damage by nitrous oxide and xenon. J Cereb Blood Flow Metab. 2003;23(10):1168–73.PubMedCrossRefGoogle Scholar
  86. 86.
    Haelewyn B, David HN, Rouillon C, Chazalviel L, Lecocq M, Risso JJ, et al. Neuroprotection by nitrous oxide: facts and evidence. Crit Care Med. 2008;36(9):2651–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Taninishi H, Takeda Y, Kobayashi M, Sasaki T, Arai M, Morita K. Effect of nitrous oxide on neuronal damage and extracellular glutamate concentration as a function of mild, moderate, or severe ischemia in halothane-anesthetized gerbils. Anesthesiology. 2008;108(6):1063–70.PubMedCrossRefGoogle Scholar
  88. 88.
    Pasternak JJ, McGregor DG, Lanier WL, Schroeder DR, Rusy DA, Hindman B, et al. Effect of nitrous oxide use on long-term neurologic and neuropsychological outcome in patients who received temporary proximal artery occlusion during cerebral aneurysm clipping surgery. Anesthesiology. 2009;110(3):563–73.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Nehls DG, Todd MM, Spetzler RF, Drummond JC, Thompson RA, Johnson PC. A comparison of the cerebral protective effects of isoflurane and barbiturates during temporary focal ischemia in primates. Anesthesiology. 1987;66(4):453–64.PubMedCrossRefGoogle Scholar
  90. 90.
    Warner DS, Takaoka S, Wu B, Ludwig PS, Pearlstein RD, Brinkhous AD, et al. Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia. Anesthesiology. 1996;84(6):1475–84.PubMedCrossRefGoogle Scholar
  91. 91.
    Gisvold SE, Safar P, Hendrickx HH, Rao G, Moossy J, Alexander H. Thiopental treatment after global brain ischemia in pigtailed monkeys. Anesthesiology. 1984;60(2):88–96.PubMedCrossRefGoogle Scholar
  92. 92.
    Bleyaert AL, Nemoto EM, Safar P, Stezoski SM, Mickell JJ, Moossy J, et al. Thiopental amelioration of brain damage after global ischemia in monkeys. Anesthesiology. 1978;49(6):390–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Smith DS, Rehncrona S, Westerberg E, Akesson B, Siesjo BK. Lipid peroxidation in brain tissue in vitro: antioxidant effects of barbiturates. Acta Physiol Scand. 1979;105(4):527–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Markowitz GJ, Kadam SD, Smith DR, Johnston MV, Comi AM. Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice. Epilepsy Res. 2011;94(3):138–48. doi: 10.1016/j.eplepsyres.2011.01.002.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Hudetz JA, Pagel PS. Neuroprotection by ketamine: a review of the experimental and clinical evidence. J Cardiothorac Vasc Anesth. 2010;24(1):131–42.PubMedCrossRefGoogle Scholar
  96. 96.
    Jensen ML, Auer RN. Ketamine fails to protect against ischaemic neuronal necrosis in the rat. Br J Anaesth. 1988;61(2):206–10.PubMedCrossRefGoogle Scholar
  97. 97.
    Ridenour TR, Warner DS, Todd MM, Baker MT. Effects of ketamine on outcome from temporary middle cerebral artery occlusion in the spontaneously hypertensive rat. Brain Res. 1991;565(1):116–22.PubMedCrossRefGoogle Scholar
  98. 98.
    Engelhard K, Werner C, Eberspacher E, Bachl M, Blobner M, Hildt E, et al. The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats. Anesth Analg. 2003;96(2):524–31.PubMedGoogle Scholar
  99. 99.
    Winkelheide U, Lasarzik I, Kaeppel B, Winkler J, Werner C, Kochs E, et al. Dose-dependent effect of S(+) ketamine on post-ischemic endogenous neurogenesis in rats. Acta Anaesthesiol Scand. 2009;53(4):528–33.PubMedCrossRefGoogle Scholar
  100. 100.
    Nurse S, Corbett D. Neuroprotection after several days of mild, drug-induced hypothermia. J Cereb Blood Flow Metab. 1996;16(3):474–80.PubMedCrossRefGoogle Scholar
  101. 101.
    Zhang L, Mitani A, Yanase H, Kataoka K. Continuous monitoring and regulating of brain temperature in the conscious and freely moving ischemic gerbil: effect of MK-801 on delayed neuronal death in hippocampal CA1. J Neurosci Res. 1997;47(4):440–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Pohorecki R, Becker GL, Reilly PJ, Landers DF. Ischemic brain injury in vitro: protective effects of NMDA receptor antagonists and calmidazolium. Brain Res. 1990;528(1):133–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Cai J, Hu Y, Li W, Li L, Li S, Zhang M, et al. The neuroprotective effect of propofol against brain ischemia mediated by the glutamatergic signaling pathway in rats. Neurochem Res. 2011;36(10):1724–31.PubMedCrossRefGoogle Scholar
  104. 104.
    Basu S, Miclescu A, Sharma H, Wiklund L. Propofol mitigates systemic oxidative injury during experimental cardiopulmonary cerebral resuscitation. Prostaglandins Leukot Essent Fatty Acids. 2011;84(5–6):123–30.PubMedCrossRefGoogle Scholar
  105. 105.
    Engelhard K, Werner C, Eberspacher E, Pape M, Blobner M, Hutzler P, et al. Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats. Eur J Anaesthesiol. 2004;21(7):530–7.PubMedCrossRefGoogle Scholar
  106. 106.
    Wang W, Lu R, Feng DY, Liang LR, Liu B, Zhang H. Inhibition of microglial activation contributes to propofol-induced protection against post-cardiac arrest brain injury in rats. J Neurochem. 2015;134(5):892–903.PubMedCrossRefGoogle Scholar
  107. 107.
    Cui D, Wang L, Qi A, Zhou Q, Zhang X, Jiang W. Propofol prevents autophagic cell death following oxygen and glucose deprivation in PC12 cells and cerebral ischemia-reperfusion injury in rats. PLoS One. 2012;7(4):e35324.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Pittman JE, Sheng H, Pearlstein R, Brinkhous A, Dexter F, Warner DS. Comparison of the effects of propofol and pentobarbital on neurologic outcome and cerebral infarct size after temporary focal ischemia in the rat. Anesthesiology. 1997;87(5):1139–44.PubMedCrossRefGoogle Scholar
  109. 109.
    Wang H, Luo M, Li C, Wang G. Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion. J Neurochem. 2011;119(1):210–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Kochs E, Hoffman WE, Werner C, Thomas C, Albrecht RF, Schulte am Esch J. The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology. 1992;76(2):245–52.PubMedCrossRefGoogle Scholar
  111. 111.
    Ito H, Watanabe Y, Isshiki A, Uchino H. Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand. 1999;43(2):153–62.PubMedCrossRefGoogle Scholar
  112. 112.
    Yamasaki T, Nakakimura K, Matsumoto M, Xiong L, Ishikawa T, Sakabe T. Effects of graded suppression of the EEG with propofol on the neurological outcome following incomplete cerebral ischaemia in rats. Eur J Anaesthesiol. 1999;16(5):320–9.PubMedCrossRefGoogle Scholar
  113. 113.
    Ichinose K, Okamoto T, Tanimoto H, Taguchi H, Tashiro M, Sugita M, et al. A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs. Resuscitation. 2006;70(2):275–84.PubMedCrossRefGoogle Scholar
  114. 114.
    Tsai YC, Huang SJ, Lai YY, Chang CL, Cheng JT. Propofol does not reduce infarct volume in rats undergoing permanent middle cerebral artery occlusion. Acta Anaesthesiol Sin. 1994;32(2):99–104.PubMedGoogle Scholar
  115. 115.
    Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG. Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol. 1997;14(3):320–6.PubMedCrossRefGoogle Scholar
  116. 116.
    Lasarzik I, Winkelheide U, Stallmann S, Orth C, Schneider A, Tresch A, et al. Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia. Anesthesiology. 2009;110(3):529–37.PubMedCrossRefGoogle Scholar
  117. 117.
    Zeng X, Wang H, Xing X, Wang Q, Li W. Dexmedetomidine protects against transient global cerebral ischemia/reperfusion induced oxidative stress and inflammation in diabetic rats. PLoS One. 2016;11(3):e0151620.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Maier C, Steinberg GK, Sun GH, Zhi GT, Maze M. Neuroprotection by the alpha-2 adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia. Anesthesiology 1993;79(2):306–12.Google Scholar
  119. 119.
    Nakano T, Okamoto H. Dexmedetomidine-induced cerebral hypoperfusion exacerbates ischemic brain injury in rats. J Anesth. 2009;23(3):378–84.PubMedCrossRefGoogle Scholar
  120. 120.
    Soonthon-Brant V, Patel PM, Drummond JC, Cole DJ, Kelly PJ, Watson M. Fentanyl does not increase brain injury after focal cerebral ischemia in rats. Anesth Analg. 1999;88(1):49–55.PubMedGoogle Scholar
  121. 121.
    Drummond JC, Cole DJ, Patel PM, Reynolds LW. Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury. Neurosurgery. 1995;37(4):742–8 .discussion 8-9PubMedCrossRefGoogle Scholar
  122. 122.
    Yuan T, Li Z, Li X, Yu G, Wang N, Yang X. Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia. J Surg Res. 2014;192(1):150–62.PubMedCrossRefGoogle Scholar
  123. 123.
    Block L, Jorneberg P, Bjorklund U, Westerlund A, Biber B, Hansson E. Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes. Eur J Neurosci. 2013;38(11):3669–78.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Upton RN, Rasmussen M, Grant C, Martinez AM, Cold GE, Ludbrook GL. Pharmacokinetics and pharmacodynamics of indomethacin: effects on cerebral blood flow in anaesthetized sheep. Clin Exp Pharmacol Physiol. 2008;35(3):317–23.PubMedCrossRefGoogle Scholar
  125. 125.
    Park EM, Cho BP, Volpe BT, Cruz MO, Joh TH, Cho S. Ibuprofen protects ischemia-induced neuronal injury via up-regulating interleukin-1 receptor antagonist expression. Neuroscience. 2005;132(3):625–31.PubMedCrossRefGoogle Scholar
  126. 126.
    Cho HJ, Staikopoulos V, Furness JB, Jennings EA. Inflammation-induced increase in hyperpolarization-activated, cyclic nucleotide-gated channel protein in trigeminal ganglion neurons and the effect of buprenorphine. Neuroscience. 2009;162(2):453–61.PubMedCrossRefGoogle Scholar
  127. 127.
    Jacobsen KR, Fauerby N, Raida Z, Kalliokoski O, Hau J, Johansen FF, et al. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice. Comp Med. 2013;63(2):105–13.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Yulug B, Cam E, Yildiz A, Kilic E. Buprenorphine does not aggravate ischemic neuronal injury in experimental focal cerebral ischemia. J Neuropsychiatry Clin Neurosci. 2007;19(3):331–4.PubMedCrossRefGoogle Scholar
  129. 129.
    Bhardwaj A, Castro IA, Alkayed NJ, Hurn PD, Kirsch JR. Anesthetic choice of halothane versus propofol: impact on experimental perioperative stroke. Stroke. 2001;32(8):1920–5.PubMedCrossRefGoogle Scholar
  130. 130.
    Kapinya KJ, Lowl D, Futterer C, Maurer M, Waschke KF, Isaev NK, 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.PubMedCrossRefGoogle Scholar
  131. 131.
    Payne RS, Akca O, Roewer N, Schurr A, Kehl F. Sevoflurane-induced preconditioning protects against cerebral ischemic neuronal damage in rats. Brain Res. 2005;1034(1–2):147–52.PubMedCrossRefGoogle Scholar
  132. 132.
    Ding XD, Zheng NN, Cao YY, Zhao GY, Zhao P. Dexmedetomidine preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest. Int J Neurosci. 2016;126(3):249–56.PubMedCrossRefGoogle Scholar
  133. 133.
    Liu JH, Feng D, Zhang YF, Shang Y, Wu Y, Li XF, et al. Chloral hydrate preconditioning protects against ischemic stroke via upregulating Annexin A1. CNS Neurosci Ther. 2015;21(9):718–26.PubMedCrossRefGoogle Scholar
  134. 134.
    Li L, Zuo Z. Isoflurane preconditioning improves short-term and long-term neurological outcome after focal brain ischemia in adult rats. Neuroscience. 2009;164(2):497–506.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Ye R, Yang Q, Kong X, Li N, Zhang Y, Han J, et al. Sevoflurane preconditioning improves mitochondrial function and long-term neurologic sequelae after transient cerebral ischemia: role of mitochondrial permeability transition. Crit Care Med. 2012;40(9):2685–93.PubMedCrossRefGoogle Scholar
  136. 136.
    Li C, Han D, Zhang F, Zhou C, Yu HM, Zhang GY. Preconditioning ischemia attenuates increased neurexin-neuroligin1-PSD-95 interaction after transient cerebral ischemia in rat hippocampus. Neurosci Lett. 2007;426(3):192–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Zhao P, Ji G, Xue H, Yu W, Zhao X, Ding M, et al. Isoflurane postconditioning improved long-term neurological outcome possibly via inhibiting the mitochondrial permeability transition pore in neonatal rats after brain hypoxia-ischemia. Neuroscience. 2014;280:193–203.PubMedCrossRefGoogle Scholar
  138. 138.
    Lai Z, Zhang L, Su J, Cai D, Xu Q. Sevoflurane postconditioning improves long-term learning and memory of neonatal hypoxia-ischemia brain damage rats via the PI3K/Akt-mPTP pathway. Brain Res. 2016;1630:25–37.PubMedCrossRefGoogle Scholar
  139. 139.
    Cole DJ, Drummond JC, Shapiro HM, Zornow MH. Influence of hypotension and hypotensive technique on the area of profound reduction in cerebral blood flow during focal cerebral ischaemia in the rat. Br J Anaesth. 1990;64(4):498–502.PubMedCrossRefGoogle Scholar
  140. 140.
    Sukhotinsky I, Dilekoz E, Moskowitz MA, Ayata C. Hypoxia and hypotension transform the blood flow response to cortical spreading depression from hyperemia into hypoperfusion in the rat. J Cereb Blood Flow Metab. 2008;28(7):1369–76.PubMedCrossRefGoogle Scholar
  141. 141.
    Sukhotinsky I, Yaseen MA, Sakadzic S, Ruvinskaya S, Sims JR, Boas DA, et al. Perfusion pressure-dependent recovery of cortical spreading depression is independent of tissue oxygenation over a wide physiologic range. J Cereb Blood Flow Metab. 2010;30(6):1168–77.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ulrike Hoffmann
    • 1
  • Huaxin Sheng
    • 1
  • Cenk Ayata
    • 2
  • David S. Warner
    • 1
    Email author
  1. 1.Multidisciplinary Neuroprotection Laboratories, Department of AnesthesiologyDuke University Medical CenterDurhamUSA
  2. 2.Neurovascular Research Laboratory, Departments of Radiology and NeurologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA

Personalised recommendations