Pharmacological Advances in Cerebrovascular Protection

  • Midori A Yenari
  • Gary K Steinberg


Recent research in the area of ischemic brain injury has provided a better basic understanding of the events leading to cell death. This work has also permitted the development of a variety of strategies that may prevent or reverse brain ischemia. Such strategies may have applications in preventing cerebral ischemic injury in high-risk neurosurgical or cardiovascular patients as well as treatment of stroke patients. This chapter reviews the pathophysiology of ischemic brain injury as well as current and future neuroprotectants as they relate to potential clinical use. Classes of compounds reviewed include barbiturates, calcium antagonists, glutamate antagonists, 21-aminosteroids, citicholine, lubeluzole, and mild hypothermia.


Cerebral Ischemia Acute Ischemic Stroke Focal Cerebral Ischemia NMDA Antagonist Global Ischemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Silver B, Weber J, Fisher M: Medical therapy for ischemic stroke.Clin Neuropharmacol1996, 19:101–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Dawson TM, Dawson VL: Protection of the brain from ischemia. InCerebrovascular Disease. Edited by Batjer HH, Caplan LR, Reiberg L,et al. Philadelphia: Lipincott Raven; 1997:319–325.Google Scholar
  3. 3.
    Albers GW. Mechanisms of injury to the central nervous system. InIntraoperative Neuroprotection. Edited by Andrews RJ. Philadelphia: Williams and Wilkins; 1996:7–19.Google Scholar
  4. 4.
    Lipton SA, Rosenberg PA: Excitatory amino acids as a final common pathway for neurologic disorders.N Engl J Med1994, 330:613–622.PubMedCrossRefGoogle Scholar
  5. 5.
    Warner DS, Zhou JG, Ramani R,et al.: Reversible focal ischemia in the rat: Effects of halothane, isoflurane, and methohexital anesthesia.J Cereb Blood Flow Metab1991, 11:794–802.PubMedCrossRefGoogle Scholar
  6. 6.
    Shiu GK, Nemoto EM: Barbiturate attenuation of brain free fatty acid liberation during global ischemia.J Neurochem1981, 37:1448–1456.PubMedCrossRefGoogle Scholar
  7. 7.
    Smith DS, Rehncrona S, Siesjo BK: Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro.Acta Physiol Scand Suppl1980, 492:129–134.PubMedGoogle Scholar
  8. 8.
    Hoff IT, Smith AL, Hankinson HL,et al.: Barbiturate protection from cerebral infarction in primates.Stroke1975, 6:28–33.PubMedCrossRefGoogle Scholar
  9. 9.
    Warner DS, Takaoka S, Wu B,et al.: Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia.Anesthesiology1996, 84:1475–1484.PubMedCrossRefGoogle Scholar
  10. 10.
    Michenfelder JD, Milde JH, Sundt TM, Jr. Cerebral protection by barbiturate anesthesia: Use after middle cerebral artery occlusion in Java monkeys.Arch Neurol1976, 33:345–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Selman WR, Spetzler RF, Roessmann UR, et al.: Barbiturate-induced coma therapy for focal cerebral ischemia: Effect after temporary and permanent MCA occlusion. J Neurosurg 1981,55:220-226PubMedCrossRefGoogle Scholar
  12. 12.
    Selman WR, Spetzler RF, Roski RA,et al.: Barbiturate coma in focal cerebral ischemia: Relationship of protection to timing of therapy.J Neurosurg1982,56:685–690.Google Scholar
  13. 13.
    Kuroiwa T, Bonnekoh P, Hossmann KA: Therapeutic window of CAl neuronal damage defined by an ultrashort -acting barbiturate after brain ischemia in gerbils.Stroke1990, 21:1489–1493.PubMedCrossRefGoogle Scholar
  14. 14.
    Drummond JC, Cole DJ, Patel PM,et al.: Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: A comparison of the extent of cerebral injury.Neurosurgery1995,37:742–748.PubMedCrossRefGoogle Scholar
  15. 15.
    Sano T, Patel PM, Drummond JC,et al.: A comparison of the cerebral protective effects of etomidate, thiopental, and isoflurane in a model of forebrain ischemia in the rat.Anesth Analg1993,76:990–997.PubMedCrossRefGoogle Scholar
  16. 16.
    Guo J, White JA, Batjer HH: The protective effects of thiopental on brain stem ischemia.Neurosurgery1995, 37:490–495PubMedCrossRefGoogle Scholar
  17. 17.
    Steen PA, Milde JH, Michenfelder JD: No barbiturate protection in a dog model of complete cerebral ischemia.Ann Neurol1979, 5:343–349.PubMedCrossRefGoogle Scholar
  18. 18.
    Pulsinelli WA, Rawlinson D, Plum F,et al.: Barbiturate exacerbation of ischemic brain damage following bilateral hemispheric ischemia in the rat.Trans Am Neurol Assoc1979,104:144–147.PubMedGoogle Scholar
  19. 19.
    Gelb AW, Floyd P, Lok P,et al.:Aprophylactic bolus of thiopentone does not protect against prolonged focal cerebral ischaemia.Can Anaesth Soc J1986, 33: 173–177.PubMedCrossRefGoogle Scholar
  20. 20.
    Nehls DG, Todd MM, Spetzler RF,et al.: A comparison of the cerebral protective effects ofisoflurane and barbiturates during temporary focal ischemia in primates. Anesthesiology 1987, 66:453–464.PubMedCrossRefGoogle Scholar
  21. 21.
    Milde LN, Milde JH, Lanier WL,et al.: Comparison of the effects of isoflurane and thiopental on neurologic outcome and neuropathology after temporary focal cerebral ischemia in primates.Anesthesiology1988,69:905–913.PubMedCrossRefGoogle Scholar
  22. 22.
    Todd MM, Chadwick HS, Shapiro HM,et al.: The neurologic effects of thiopental therapy following experimental cardiac arrest in cats.Anesthesiology1982, 57:76–86.PubMedCrossRefGoogle Scholar
  23. 23.
    Mutch WA, Graham MR, Halliday WC,et al.: Paraplegia following thoracic aortic Gross-clamping in dogs: No difference in neurologica outcome with a barbiturate versus isoflurane.Stroke1993, 24: 1554–1559.PubMedCrossRefGoogle Scholar
  24. 24.
    Spetzler RF, Hadley MN: Protection against cerebral ischemia: the role of barbiturates.Cerebrovasc Brain Metab Rev1989,1:212–229.PubMedGoogle Scholar
  25. 25.
    Giffard RG, Jaffe RA: Anesthetic agents for neuroprotection. InIntraoperative Neuroprotection. Edited by Anreus RJ. Philadelphia: Williams and Wilkins; 1996,23–36.Google Scholar
  26. 26.
    Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: Cerebral protection by a barbiturate.Anesthesiology1986, 64:165–170.Google Scholar
  27. 27.
    Zaidan JR, Klochany A, Martin WM,et al.: Effect of thiopental on neurologic outcome following coronary artery bypass grafting.Anesthesiology1991,74:406–411.PubMedCrossRefGoogle Scholar
  28. 28.
    Brain Resuscitation Clinical Trial I Study Group. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest.Trans Am Neurol Assoc1986, 314:397–403.Google Scholar
  29. 29.
    Schwab S, Spranger M, Schwarz S,et al.: Barbiturate coma in severe hemispheric stroke: Useful or obsolete?Neurology1997, 48:1608–16l3.PubMedGoogle Scholar
  30. 30.
    Lee MW, Deppe SA, Sipperly ME,et al.: The efficacy of barbiturate coma in the management of uncontrolled intracranial hypertension following neurosurgical trauma.J Neurotrauma1994, 11:325–331.PubMedCrossRefGoogle Scholar
  31. 31.
    Ward JD, Becker DP, Miller JD,et al.: Failure of prophylactic barbiturate coma in the treatment of severe head injury.J Neurosurg1985, 62:383–388.PubMedCrossRefGoogle Scholar
  32. 32.
    Eisenberg HM, Frankowski RF, Contant CF,et al.: Highdose barbiturate control of elevated intracranial pressure in patients with severe head injury.J Neurosurg1988, 69:15–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Schalen W, Messeter K, Nordstrom CH: Complications and side effects during thiopentone therapy in patients with severe head injuries.Acta Anaesthesiol Scand1992, 36:369–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Sato M, Tanaka S, Suzuki K,et al.: Complications associated with barbiturate therapy.Resuscitation1989, 17:233–24l.PubMedCrossRefGoogle Scholar
  35. 35.
    Barone FC, Feuerstein GZ, Spera RPA: Calcium channel blockers in cerebral ischemia.Exp Opin Invest Drugs1997,6:502–529. Recent review of calcium channel blockers.CrossRefGoogle Scholar
  36. 36.
    The American Nimodipine Study Group: Clinical trial of nimodipine in acute ischemic stroke.Stroke1992, 23:3–8.Google Scholar
  37. 37.
    Gelmers HJ, Gorter K, de Weerdt CJ,et al.: A controlled trial ofnimodipine in acute ischemic stroke.N EnglJ Med1988,318:203–207.CrossRefGoogle Scholar
  38. 38.
    Kaste M, Fogelholm R, Erila T,et al.: A randomized, double-blind, placebo-controlled trial ofnimodipine in acute ischemic hemispheric stroke.Stroke1994, 25: 1348–1353.PubMedCrossRefGoogle Scholar
  39. 39.
    Petruk KC, West M, Mohr G,et al.: Nimodipine treatment in poor-grade aneurysm patients: Results of a multicenter double-blind placebo-controlled trial.J Neurosurg1988, 68:505–517.PubMedCrossRefGoogle Scholar
  40. 40.
    Pickard JD, Murray GD, Illingworth R,et al.: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial.BMJ1989, 298:636–642.PubMedCrossRefGoogle Scholar
  41. 41.
    Allen GS, Ahn HS, Preziosi TJ,et al.: Cerebral arterial spasm: A controlled trial of nimodipine in patients with subarachnoid hemorrhage.N Engl J Med1983,308:619–624.PubMedCrossRefGoogle Scholar
  42. 42.
    Davalos A, Cendra E, Gonzales B,et al.: Double blind, randomized clinical trial of nicardipine vs placebo in acute ischemic stroke: Preliminary results [abstract].14th World Congress of Neurology; 1989. New York: Excerpta Medica; 1991.Google Scholar
  43. 43.
    Rosenbaum D, Zabramski J, Frey J,et al.: Early treatment of ischemic stroke with a calcium antagonist. Stroke 1991, 22:437–44l.PubMedCrossRefGoogle Scholar
  44. 44.
    Haley EC, Jr., Kassell NF, Tomer JC: A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage: A report of the Cooperative Aneurysm Study.J Neurosurg1993, 78:537–547.PubMedCrossRefGoogle Scholar
  45. 45.
    Haley EC, Jr., Kassell NF, Tomer JC: A randomized trial of nicardipine in subarachnoid hemorrhage: Angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study.J Neurosurg1993, 78:548–553.PubMedCrossRefGoogle Scholar
  46. 46.
    Tsien RW, Lipscombe D, Madison DV,et al.: Multiple types of neuronal calcium channels and their selective modulation.Trends Neurosci1988, 11:431–438.CrossRefGoogle Scholar
  47. 47.
    Olivera BM, Gray WR, Zeikus R,et al.: Peptide neurotoxins from fish-hunting cone snails.Science1985, 230:l338-l343.PubMedCrossRefGoogle Scholar
  48. 48.
    Hillyard DR, Monje VD, Mintz IM,et al.: A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron1992, 9:69–77.PubMedCrossRefGoogle Scholar
  49. 49.
    Buchan AM, Gertler SZ, Li H,et al.: A selective N -type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia.J Cereb Blood Flow Metab1994, 14:903–910.PubMedCrossRefGoogle Scholar
  50. 50.
    Takizawa S, Matsushima K, Fujita H,et al.: A selective Ntype calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia.J Cereb Blood Flow Metab1995, 15:611–618.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhao Q, Smith ML, Siesjo BK: The omega-conopeptide SNX-111, an N-type calcium channel blocker, dramatically ameliorates brain damage due to transient focal ischaemia.Acta Physiol Scand1994, 150:459–461.PubMedCrossRefGoogle Scholar
  52. 52.
    Smith M-L, Siesjo BK: Postischemia treatment with the omega -conopeptide SNX-111 protects the rat brain against ischemic damage. InPharmacology of Cerbral Ischemia. Edited by Krieglstein J, Oberpilcher H. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 1992: 161–167Google Scholar
  53. 53.
    Valentino K, Newcomb R, Gadbois T,et al.: A selective Ntype calcium channel antagonist protects against neuronal loss after global cerebral ischemia.Proc Natl Acad Sci USA1993, 90:7894–7897.PubMedCrossRefGoogle Scholar
  54. 54.
    Verweij BH, Muizelaar JP, Vinas FC,et al.: Mitochondrial dysfunction after experimental and human brain injury and its possible reversal with. a selective N-type calcium channel antagonist (SNX-111).Neurol Res1997, 19:334–339.PubMedGoogle Scholar
  55. 55.
    Hovda DA, Fu K, Badie H,et al.: Administration of an omega-conopeptide one hour following traumatic brain injury reduces 45calcium accumulation.Acta Neurochir Suppl1994, 60:521–523.Google Scholar
  56. 56.
    Steinberg GK, George CP, DeLaPaz R,et al.: Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits.Stroke1988, 19:1112–1118.PubMedCrossRefGoogle Scholar
  57. 57.
    Steinberg GK, Saleh J, Kunis D: Delayed treatment with dextromethorphan and dextrorphan reduces cerebral damage after transient focal ischemia.Neurosci Lett1988, 89:193–197.PubMedCrossRefGoogle Scholar
  58. 58.
    Perez-Pinzon MA, Maier CM, Yoon EJ,et al.: Correlation of CGS 19755 neuroprotection against in vitro excitotoxicity and focal cerebral ischemia.J Cereb Blood Flow Metab1995, 15:865–876.CrossRefGoogle Scholar
  59. 59.
    Perez-Pinzon M, Yenari M, Sun G,et al.: SNX-111 in a rabbit model of focal ischemia.J Neurol Sci1997, 153:25–31.PubMedCrossRefGoogle Scholar
  60. 60.
    Yenari MA, Palmer IT, Sun GH,et al.: Time-course and treatment response with SNX-111, an N-type calcium channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted MRI.Brain Res1996, 739:36–45.PubMedCrossRefGoogle Scholar
  61. 61.
    Pringle A, Benham C, Sim L,et al.: Selective N -type calcium channel antagonist omega conotoxin MVIIA is neuroprotective against hypoxic neurodegeneration in organotypic hippocampal-slice cultures.Stroke1996, 27:2124–2130.PubMedCrossRefGoogle Scholar
  62. 62.
    Madden KP, Clark WM, Marcoux FW,et al.: Treatment with conotoxin, an "N-type" calcium channel blocker, in neuronal hypoxic-ischemic injury.Brain Res1990, 537:256–262.PubMedCrossRefGoogle Scholar
  63. 63.
    Mcguire D, Kugler A, Bowersox S: SNX-111: The firstNtype, voltage-sensitive calcium channel antagonist administered to human. Pharmacokinetics and evidence of drug effect [abstract].Neurology1996, 46:A203.Google Scholar
  64. 64.
    Choi DW: Glutamate neurotoxicity and diseases of the nervous system.Neuron1988, 1:623–634.PubMedCrossRefGoogle Scholar
  65. 65.
    Albers GW. Potential therapeutic uses ofN-Methyl-DAspartate antagonists in cerebral ischemia.Clin Neuropharmacoll990, 13:177–197.CrossRefGoogle Scholar
  66. 66.
    Foster AC, Fagg GE: Neurobiology: Taking apart NMDA receptors.Nature1987,329:395–396.PubMedCrossRefGoogle Scholar
  67. 67.
    Gill R: The pharmacology of alpha-amino-3-hydroxy-5- methyl-4-isoxazole propionate (AMPA) Ikainate antagonists and their role in cerebral ischaemia.Cerebrovasc Brain Metab Rev1994, 6:225–256.PubMedGoogle Scholar
  68. 68.
    Goldberg MP, Pham PC, Choi DW: Dextrorphan and dextromethorphan attenuate hypoxic injury in neuronal culture. Neurosci Lett1987, 80: 11–15.PubMedCrossRefGoogle Scholar
  69. 69.
    Steinberg GK, Saleh J. Kunis D,et al.: Protective effect of N -Methyl-D-Aspartate antagonists after focal cerebral ischemia in rabbits.Stroke1989, 20:1247–1252.PubMedCrossRefGoogle Scholar
  70. 70.
    van Rijen PC, Verheul HB, van Echteld al.: Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy.Stroke1991, 22:343–350.PubMedCrossRefGoogle Scholar
  71. 71.
    Tortella FC, Martin DA, Allot CP,et al.: Dextromethorphan attenuates post-ischemic hypoperfusion following incomplete global ischemia in the anesthetized rat.Brain Res1989, 482:179–183.PubMedCrossRefGoogle Scholar
  72. 72.
    Steinberg GK, Kunis D, DeLaPaz R,et al.: Neuroprotection following focal cerebral ischaemia with the NMDA antagonist dextromethorphan, has a favourable dose response profile.Neurol Res1993,15:174–180.PubMedGoogle Scholar
  73. 73.
    Steinberg GK, Kunis D, Saleh J,et al.: Protection after transient focal cerebral ischemia by the N-Methyl-D-Aspartate antagonist dextrorphan is dependent upon plasma and brain levels.J Cereb Blood Flow Metab1991, 11:1015–1024.PubMedCrossRefGoogle Scholar
  74. 74.
    OLney JW, Labruyere J. Price MT: Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.Science1989,244:1360–1362.PubMedCrossRefGoogle Scholar
  75. 75.
    Sharp FR, Jasper P, Hall al.: MK-801 and ketamine induce heat shock protein HSP72 in injured neurons in posterior cingulate and retrosplenial cortex.Ann Neurol1991,30:801–809.PubMedCrossRefGoogle Scholar
  76. 76.
    Sharp FR, Butman M, Aardalen K,et al.: Neuronal injury produced by NMDA antagonists can be detected using heat shock proteins and can be blocked with antipsychotics.Psychopharmacol Bull1994, 30:555–560.PubMedGoogle Scholar
  77. 77.
    Nakki R, Nickolenko J, Chang J,et al.: Haloperidol prevents ketamine and phencyclidine-induced HSP70 protein expression but not microglial activation.Exp Neurol1996,137:234–241.PubMedCrossRefGoogle Scholar
  78. 78.
    Sharp FR, Butman M, Wang S,et al.: Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine.J Neurosci Res1992, 33:605–616.PubMedCrossRefGoogle Scholar
  79. 79.
    Muir KW, Lees KR: Clinical experience with excitatory amino acid antagonist drugs.Stroke1995,26:503–513. 80. Albers GW, Saenz RE, Moses J Jr.,et al.: Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. Stroke 1991,22:1075–1077.PubMedCrossRefGoogle Scholar
  80. 81.
    Albers GW, Saenz RE, Moses J Jr.: Tolerability of oral dextromethorphan in patients with a history of brain ischemia.Clin Neuropharmacol1992, 15:509$#x2013;514.PubMedCrossRefGoogle Scholar
  81. 82.
    Hollander D, Pradas J, Kaplan R,et al.: High-dose dextromethorphan in amyotrophic lateral sclerosis: Phase I safety and pharmacokinetic studies.Ann Neurol1994, 36:920–924.PubMedCrossRefGoogle Scholar
  82. 83.
    Steinberg GK, Bell TE, Yenari MA: Dose escalation safety and tolerance study of the N-Methyl-D-Aspartate antagonist dextromethorphan inNeurosurgerypatients.J Neurosurg1996,84: 860–6.PubMedCrossRefGoogle Scholar
  83. 84.
    Albers GW, Atkinson RP, Kelley RE,et al.: Safety, tolerability, and pharmakokinetics of the N-Methyl-D-Aspartate antagonist dextrorphan in patients with acute stroke.Stroke1995, 26:254–258.PubMedCrossRefGoogle Scholar
  84. 85.
    Shuaib A, Ijaz S, Mazagri R,et al.: CGS-19755 is neuroprotective during repetitive ischemia: this effect is significantly enhanced when combined with hypothermia.Neuroscience1993,56:915–920.CrossRefGoogle Scholar
  85. 86.
    Ohno M, Yamamoto T, Ueki S,et al.: Protection byNMethyl- D-Aspartate receptor antagonists against impairment of working memory in rats following transient cerebral ischemia.Neurosci Lett1992, 138: 1–4.PubMedCrossRefGoogle Scholar
  86. 87.
    Swan JH, Meldrum BS: Protection by NMDA antagonists against selective cell loss following transient ischaemia.J Cereb Blood Flow Metab1990, 10:343–351.PubMedCrossRefGoogle Scholar
  87. 88.
    Takizawa S, Hogan M, Hakim AM: The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia.J Cereb Blood Flow Metab1991,11:786–793.CrossRefGoogle Scholar
  88. 89.
    Steinberg GK, Perez-Pinzon MA, Maier CM,et al.: CGS 19755 (selfotel): Correlation of in vitro neuroprotection, protection against experimental ischemia and CSF levels in cerebrovascular surgery patients. InPharmacology of Cerebral Ischemia. Edited by Krieglstein J, Oberpichler Schwenk H. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH; 1994:225–232.Google Scholar
  89. 90.
    Grotta J, Clark W, Coull B,et al.: Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke: Results of a phase IIa randomized trial.Stroke1995, 26:602–605.CrossRefGoogle Scholar
  90. 91.
    Yenari MA, Kotake A, Powell M,et al.: Dose escalation safety and tolerance study of the competitive NMDA antagonist, Selfotel (CGS 19755) in neurosurgery patients.Clin Neuropharmacol1998, in press.Google Scholar
  91. 92.
    Davis SM, Albers GW, Diener H-C,et al.: Termination of acute stroke studies involving selfotel treatment [letter].Lancet1997,349:32.PubMedCrossRefGoogle Scholar
  92. 93.
    Edwards K: Group tC-S: Cerestat (aptiganel hydrochloride) in the treatment of acute ischemic stroke: Results of a phase II trial.Neurology1996, 46:A424.Google Scholar
  93. 94.
    Muir KW, Grosset DG, Gamzu E,et al.: Pharmacological effects of the non-competitive NMDA antagonist CNS 1102 in normal volunteers.Br J Clin Pharmacol1994, 38:33–38.PubMedGoogle Scholar
  94. 95.
    Muir KW, Grosset DG, Lees KR: Clinical pharmacology of CNS 1102 in volunteers.Ann N Y Acad Sci1995, 765:279–289.PubMedCrossRefGoogle Scholar
  95. 96.
    Muir KW, Grosset DG, Lees KR: Clinical pharmacology of CNS 1102 in man.Ann N Y Acad Sci1995,765:336–337.PubMedCrossRefGoogle Scholar
  96. 97.
    Grosset DG, Muir KW, Lees KR: Systemic and cerebral hemodynamic responses to the noncompetitive N-Methyl- D-Aspartate (NMDA) antagonist CNS 1102.J Cardiovasc Pharmacol1995, 25:705–709.CrossRefGoogle Scholar
  97. 98.
    Wagstaff A, Teasdale GM, Clifton G,et al.: The cerebral hemodynamic and metabolic effects of the noncompetitive NMDA antagonist CNS 1102 in humans with severe head injury.Ann N Y Acad Sci1995, 765:332–333.PubMedCrossRefGoogle Scholar
  98. 99.
    Warach S, Benfield A, Schlaug G,et al.: Stroke therapy evaluated by diffusion weighted imaging: A pilot study of the neuroprotective effect of CERESTAT, a noncompetitive N-Methyl-D-Aspartate receptor antagonist, in human stroke [abstract].Proceedings of the Society of Magnetic Resonance. New York: Society of Magnetic Resonance; 1996, 5:90.Google Scholar
  99. 100.
    Johnson IW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons.Nature1987, 325:529–531.PubMedCrossRefGoogle Scholar
  100. 101.
    Hawkinson JE, Huber KR, Sahota PS,et al.: The N-MethylD- Aspartate (NMDA) receptor glycine site antagonist ACEA 1021 does not produce pathological changes in rat brain.Brain Res1997,744:227–234.CrossRefGoogle Scholar
  101. 102.
    Berger P, Farrel K, Sharp F,et al.: Drugs acting at the strychnine-insensitive glycine receptor do not induce HSP-70 protein in the cingulate cortex.Neurosci Lett1994,168:147–150.PubMedCrossRefGoogle Scholar
  102. 103.
    Whitehouse MJ, Navalta L, Densel M,et al.: Initial clinical experience with ACEA 1021: Safety, tolerance, and pharmacokinetics in healthy volunteers [abstract].1996 North American Stroke Meeting. Denver: National Stroke Association; 1996.Google Scholar
  103. 104.
    Yenari MA, Tong DC, Albers GW: Glycine antagonists for treatment of ischemic brain injury. InClinical Pharmacology of Cerebral Ischemia. Totowa, NJ: Humana Press; 1997:127–151.Google Scholar
  104. 105.
    Koek W, Colpaert FC. Selective blockade of N -Methyl-DAspartate (NMDA) -induced convulsions by NMDA antagonists and putative glycine antagonists: Relationship with phencyclidine-like behavioral effects.J Pharmacol Exp Ther1990,252:349–357.PubMedGoogle Scholar
  105. 106.
    Chen J, Graham S, Moroni F,et al.: A study ofthe dose dependency of a glycine receptor antagonist in focal ischemia.J Pharmacol Exp Ther1993,267:937–941.PubMedGoogle Scholar
  106. 107.
    Warner DS, Martin H, Ludwig P,et al.: In vivo models of cerebral ischemia: effects of parenterally administered NMDA receptor glycine site antagonists.J Cereb Blood Flow Metab1995, 15:188–196.PubMedCrossRefGoogle Scholar
  107. 108.
    Takaoka S, Bart RD, Pearlstein R,et al.: Neuroprotective effect of NMDA receptor glycine recognition site antagonism persists when brain temperature is controlled.J Cereb Blood Flow Metab1997,17:161–167.PubMedCrossRefGoogle Scholar
  108. 109.
    Pellegrini-Giampietro DE, Cozzi A, Moroni F: The glycine antagonist and free radical scavenger 7-Cl-thio-kynurenate reduces CAl ischemic damage in the gerbil.Neuroscience1994, 63:701–709.PubMedCrossRefGoogle Scholar
  109. 110.
    Wood ER, Bussey TJ, Phillips AG: A glycine antagonist reduces ischemia-induced CAl cell loss in vivo.Neurosci Lett1992, 145:10–14.PubMedCrossRefGoogle Scholar
  110. 111.
    Smith DH, Okiyama K, Thomas MJ,et al.: Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury.J Neurosci1993, 13:5383–5392.PubMedGoogle Scholar
  111. 112.
    Tsuchida E, Bullock R: The effect of the glycine site-specific N-Methyl-D-Aspartate antagonist ACEA1021 on ischemic brain damage caused by acute subdural hematoma in the rat.J Neurotrauma1995, 12:279–288.CrossRefGoogle Scholar
  112. 113.
    McDonald IW, Johnston MV: Pharmacology of N-MethylD- Aspartate-induced brain injury in an in vivo perinatal rat model.Synapse1990, 6: 179–188.PubMedCrossRefGoogle Scholar
  113. 114.
    Tanaka H, Yasuda H, Kato T,et al.: Neuroprotective and anticonvulsant actions of SM -18400, a novel strychnineinsensitive glycine site antagonist.J Cereb Blood Flow Metab1995, 15:S431.Google Scholar
  114. 115.
    Yasuda H, Tanaka H, Ohtani K,et al.: Neuroprotective effects of a novel NMDA glycine site antagonist, SM- 18400, in the rat model of cerebral ischemia.Society for Neuroscience Abstracts1995, 21:996.Google Scholar
  115. 116.
    Bordi F, Pietra C, Ziviani L,et al.: The glycine antagonist GV150526 protects somatosensory evoked potentials and reduces the infarct area in the MCAo model of focal ischemia in the rat.Exp Neurol1997, 145:425–433.PubMedCrossRefGoogle Scholar
  116. 117.
    Takano K, Tatlisumak T, Formato JE,et al.: Glycine site antagonist attenuates irlfarct size in experimental focal ischemia: Postmortem and diffusion mapping studies.Stroke1997, 28: 1255–1262.PubMedCrossRefGoogle Scholar
  117. 118.
    Faught E, Sachdeo RC, Remler MP,et al.: Felbamate monotherapy for partial-onset seizures: An active-control trial.Neurology1993, 43:688–692.PubMedGoogle Scholar
  118. 119.
    Leppik IE, Dreifuss FE, Pledger GW,et al.: Felbamate for partial seizures: results of a controlled clinical trial.Neurology1991,41:1785–1789.PubMedGoogle Scholar
  119. 120.
    Wallis RA, Panizzon KL, Fairchild MD,et al.: Protective effects offelbamate against hypoxia in the rat hippocampal slice.Stroke1992, 23:547–551.PubMedCrossRefGoogle Scholar
  120. 121.
    Wallis RA, Panizzon KL: Glycine reversal of felbamate hypoxic protection.Neuroreport1993, 4:951–954.PubMedCrossRefGoogle Scholar
  121. 122.
    Wallis RA, Panizzon KL, Nolan JP: Glycine-induced CA1 excitotoxicity in the rat hippocampal slice.Brain Res1994,664:115–125.PubMedCrossRefGoogle Scholar
  122. 123.
    Shuaib A, Waqaar T, Ijaz MS,et al.: Neuroprotection with felbamate: a 7 and 28-day study in transient forebrain ischemia in gerbils.Brain Res1996, 727:65–70.PubMedGoogle Scholar
  123. 124.
    Bertorelli R, Smime S, Adami M,et al.: Neuroprotective effects of felbamate on global ischaemia in Mongolian gerbils.Pharmacol Res1996, 34:59–64.PubMedCrossRefGoogle Scholar
  124. 125.
    Wasterlain CG, Adams LM, Hattori H,et al.: Felbamate reduces hypoxic-ischemic brain damage in vivo.Bur J Pharmacol1992,212:275–278.Google Scholar
  125. 126.
    Wasterlain CG, Adams LM, Schwartz PH,et al.: Posthypoxic treatment with felbamate is neuroprotective in a rat model of hypoxia-ischemia.Neurology1993, 43:2303–2310.PubMedGoogle Scholar
  126. 127.
    Adusumalli VE, Wichmann JK, Kucharczyk N,et al.: Drug concentrations in human brain tissue samples from epileptic patients treated with felbamate.Drug Metab Dispos Biol Fate Chem1994, 22:168–70.PubMedGoogle Scholar
  127. 128.
    Pennell PB, Ogaily MS, Macdonald RL: Aplastic anemia in a patient receiving felbamate for complex partial seizures.Neurology1995,45:456–460.PubMedGoogle Scholar
  128. 129.
    Albers GW, Clark WM, Atkinson RP,et al.: Dose escalation study of the NMDA glycine-site antagonist ACEA 1021 in acute ischemic stroke [abstract].Stroke1997, 28:233.Google Scholar
  129. 130.
    Dyker AG, Lees KR, Preston C,et al.: The safety, tolerability and pharmacokinetics of GV150526A in patients with acute stroke [abstract].Stroke1997, 28:233.CrossRefGoogle Scholar
  130. 131.
    Lan JQ, Chen J, Sharp FR,et al.: Induction of heat-shock protein (HSP72) in the cingulate and retrosplenial cortex by drugs that antagonize the effects of excitatory amino acids.Brain Res Mol Brain Res1997, 46:297–302.PubMedCrossRefGoogle Scholar
  131. 132.
    Wang S, Yang Q, Moller CJ,et al.: Eliprodil prevents expression of the 70 kDa heat shock protein in MK801- injured neurones.Pharmacol Toxicol1996, 79:166-168.PubMedCrossRefGoogle Scholar
  132. 133.
    Patat A, Molinier P, Hergueta T,et al.: Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.Int Clin Psychopharmacol1994, 9:155–162.PubMedCrossRefGoogle Scholar
  133. 134.
    Baskaya MK, Rao AM, Donaldson D,et al.: Protective effects ofifenprodil on ischemic injury size, blood-brain barrier breakdown, and edema formation in focal cerebral ischemia.Neurosurgery1997, 40:364–370.PubMedCrossRefGoogle Scholar
  134. 135.
    Toulmond S, Serrano A, Benavides J,et al.: Prevention by eliprodil (SL 82.07l5) of traumatic brain damage in the rat: Existence of a large (18 h) therapeutic window.Brain Res1993, 620:32–41.PubMedCrossRefGoogle Scholar
  135. 136.
    Buchan AM, Lesiuk H, Barnes KA,et al.: AMPA antagonists: Do they hold more promise for clinical stroke trials than NMDA antagonists?Stroke1993, 24:1148–1152.CrossRefGoogle Scholar
  136. 137.
    Hu P, Diemer NH, Bruhn T,et al.: Effects of the AMP Areceptor antagonist, NBQX, on neuron loss in dentate hilus of the hippocampal formation after 8, 10, or 12 min of cerebral ischemia in the rat.J Cereb Blood Flow Metab1997,17:147–152.PubMedCrossRefGoogle Scholar
  137. 138.
    Graham SH, Chen J, Lan JQ,et al.: A dose-response study of neuroprotection using the AMP A antagonist NBQX in rat focal cerebral ischemia.J Pharmacol Exp Ther1996, 276:1–4.PubMedGoogle Scholar
  138. 139.
    Lo EH, Pierce AR, Mandeville JB,et al.: Neuroprotection with NBQX in rat focal cerebral ischemia: Effects on ADC probability distribution functions and diffusion-perfusion relationships.Stroke1997,28:439–446 (discussion 446–447).PubMedCrossRefGoogle Scholar
  139. 140.
    Bowes MP, Swanson S, Zivin JA: The AMPA antagonist LY293558 improves functional neurological outcome following reversible spinal cord ischemia in rabbits.J Cereb Blood Flow Metab1996, 16, 967-972.PubMedCrossRefGoogle Scholar
  140. 141.
    Bullock R, Graham DI, Swanson S,et al.: N europrotective effect of the AMP A receptor antagonist LY-293558 in focal cerebral ischemia in the cat.J Cereb Blood Flow Metab1994, 14:466–471.CrossRefGoogle Scholar
  141. 142.
    Li H, Buchan AM: Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischemia prevents CA1 neuronal injury.J Cereb Blood Flow Metab1993, 13:933–939.PubMedCrossRefGoogle Scholar
  142. 143.
    Sheardown MJ, Suzdak PD, Nordholm L:AMPA, but not NMDA, receptor antagonism is neuroprotective in gerbil global ischaemia, even when delayed 24 h.Bur J Pharmacol1993, 236:347–353.Google Scholar
  143. 144.
    Xue D, Huang ZG, Barnes K,et al.: Delayed treatment withAMPA, but not NMDA, antagonists reduces neocortical infarction.J Cereb Blood Flow Metab1994, 14:251–261.PubMedCrossRefGoogle Scholar
  144. 145.
    Shimizu-Sasamata M, Kawasaki-Yatsugi S, Okada M,et al.: YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole- 4-propionate/kainate receptor antagonist.J Pharmacal Exp Ther1996, 276:84–92.Google Scholar
  145. 146.
    Yao H, Ibayashi S, Nakane H,et al.: AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.Brain Res1997,753:80–85.PubMedCrossRefGoogle Scholar
  146. 147.
    Yatsugi S, Takahashi M, Kawasaki-Yatsugi S,et al.: Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats.J Cereb Blood Flow Metab1996, 16:959–966.PubMedCrossRefGoogle Scholar
  147. 148.
    Lyden PD: GABA and neuroprotection.Int Rev Neurobiol1997,40:233–258.PubMedCrossRefGoogle Scholar
  148. 149.
    Snape MF, Baldwin HA, Cross AJ,et al.: The effects of chlormethiazole and nimodipine on cortical infarct area after focal cerebral ischaemia in the rat.Neuroscience1993,53:837–844.PubMedCrossRefGoogle Scholar
  149. 150.
    Shuaib A, Ijaz S, Kanthan R: Clomethiazole protects the brain in transient forebrain ischemia when used up to 4h after the insult.Neurosci Lett1995, 197:109–112.PubMedCrossRefGoogle Scholar
  150. 151.
    Lyden PD, Jackson-Friedman C, Lonzo-Doktor L: Medical therapy for intracerebral hematoma with the gammaaminobutyric acid-A agonist muscimol.Stroke1997, 28:387–391.PubMedCrossRefGoogle Scholar
  151. 152.
    Lyden PD, Lonzo L: Combination therapy protects ischemic brain in rats: A glutamate antagonist plus a gamma-aminobutyric acid agonist.Stroke1994, 25: 189–196.PubMedCrossRefGoogle Scholar
  152. 153.
    Hall ED: Brain attack: Acute therapeutic interventions. Free radical scavengers and antioxidants.Neurosurg Clin N Am1997, 8:195–206.PubMedGoogle Scholar
  153. 154.
    Hall ED: Efficacy and mechanisms of action of the cyto-protective lipid percoddation inhibitor tirilazad mesylate in subarachnoid haemorrhage.Eur J Anaesthesiol1996, 13:279-289.PubMedCrossRefGoogle Scholar
  154. 155.
    Haley EC, Jr., Kassell NF, Alves WM,et al.: Phase II trial of tirilazad in aneurysmal subarachnoid hemorrhage: A report of the Cooperative Aneurysm Study.J Neurosurg1995, 82:786-790.PubMedCrossRefGoogle Scholar
  155. 156.
    The STIPAS Investigators: Safety study of tirilazad mesy-late in patients with acute ischemic stroke (STIPAS).Stroke1994, 25:418-423.Google Scholar
  156. 157.
    Fleishaker JC, Straw RN, Cross CJ: Pharmacokinetics of tirilazad and U-89678, an active, reduced metabolite, following acute head trauma in adults.J Pharm Sci1997, 86:434-437.CrossRefGoogle Scholar
  157. 158.
    Fleishaker JC, Peters GR: Pharmacokinetics of tirilazad and U-89678 in ischemic stroke patients receiving a loading regimen and maintenance regimen of 10 mg/kg/day of tirilazad.J Clin Pharmacol1996, 36:809-813.Google Scholar
  158. 159.
    Kassell NF, Haley EC Jr., Apperson-Hansen C,et al.: Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: A cooperative study in Europe, Australia, and New Zealand.J Neurosurg1996, 84:221-228.PubMedCrossRefGoogle Scholar
  159. 160.
    Haley EC Jr., Kassell NF, Apperson-Hansen C, et al.: A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America.J Neurosurg1997, 86:467-474.PubMedCrossRefGoogle Scholar
  160. 161.
    The RANTTAS Investigators. A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS).Stroke1996, 27:1453-1458.Google Scholar
  161. 162.
    Bracken MB, Shepard MJ, Holford TR,et al.: Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial.JAMA1997, 277:1597-1604.PubMedCrossRefGoogle Scholar
  162. 163.
    Weiss GB: Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline.Life Sci1995, 56:637-660.PubMedCrossRefGoogle Scholar
  163. 164.
    Schabitz WR, Weber J, Takano K,et al.: The effects of pro longed treatment with citicoline in temporary experimental focal ischemia.J Neurol Sci1996, 138:21-25.PubMedCrossRefGoogle Scholar
  164. 165.
    Clark WM, Warach SJ, Pettigrew LC,et al.: A randomized dose-response trial of citicoline in acute ischemic stroke patients.Neurology1997, 49(3):671-678.PubMedGoogle Scholar
  165. 166.
    Maiese K, TenBroeke M, Kue I: Neuroprotection of lubeluzole is mediated through the signal transduction pathways of nitric oxide.J Neurochem1997, 68:710-714.PubMedCrossRefGoogle Scholar
  166. 167.
    Lesage AS, Peeters L, Leysen JE: Lubeluzole, a novel long-term neuroprotectant, inhibits the glutamate-activated nitric oxide synthase pathway.J Pharmacol Exp Ther1996, 279:759-766.PubMedGoogle Scholar
  167. 168.
    Aronowski J, Strong R, Grotta IC: Treatment of experimental focal ischemia in rats with lubeluzole.Neuropharmacology1996, 35:689-693.PubMedCrossRefGoogle Scholar
  168. 169.
    De Ryck M, Keersmaekers R, Duytschaever H,et al.: Lubeluzole protects sensorimotor function and reduces infarct size in a photochemical stroke model in rats.Pharmacol Exp Ther1996, 279:748-758.Google Scholar
  169. 170.
    Haseldonckx M, Van Reempts J, Van de Ven M,et al.: Protection with lubeluzole against delayed ischemic brain damage in rats: A quantitative histopathologic study.Stroke1997, 28:428-432.PubMedCrossRefGoogle Scholar
  170. 171.
    Diener HC, Hacke W, Hennerici M,et al.: Lubeluzole in acute ischemic stroke: A double-blind, placebo-controlled phase II trial. Lubeluzole International Study Group.Stroke1996, 27:76-81.PubMedCrossRefGoogle Scholar
  171. 172.
    Diener HC, Kaste M, Hacke W,et al.: Lubeluzole in acute ischemic stroke [abstract].Stroke1997, 28:271.Google Scholar
  172. 173.
    Grotta J, Hantson L, Wessel T,et al.: The efficacy and safety of lubeluzole in patients with acute ischemic stroke.Stroke1997, 28:271.CrossRefGoogle Scholar
  173. 174.
    Maher J, Hachinski V: Hypothermia as a potential treatment for cerebral ischemia.Cerebrovasc Brain Metab Rev1993, 5:277-300.PubMedGoogle Scholar
  174. 175.
    Ginsberg MD, Sternau LL, Globus MY,et al.: Therapeutic modulation of brain temperature: relevance to ischemic brain injury.Cerebrovasc Brain Metab Rev1992, 4:189-225.PubMedGoogle Scholar
  175. 176.
    Baker CJ, Onesti ST, Solomon RA: Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: A time-course study.J Neurosurg1992, 77:438-444.PubMedCrossRefGoogle Scholar
  176. 177.
    Colbourne F, Corbett D: Delayed postischemic hypothermia: A six month survival study using behavioral and histological assessments of neuroprotection.J Neurosci1995, 15:7250-7260.PubMedGoogle Scholar
  177. 178.
    Dietrich WD, Busto R, Alonso 0,et al.: Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats.J Cereb Blood Flow Metab1993, 13:541-549.PubMedCrossRefGoogle Scholar
  178. 179.
    Baker AJ, Zornow MH, Grafe MR,et al.: Hypothermia pre-vents ischemia-induced increases in hippocampal glycine concentrations in rabbits.Stroke1991, 22:666-673.PubMedCrossRefGoogle Scholar
  179. 180.
    Globus MY, Alonso 0, Dietrich WD,et al.: Glutamate release and free radical production following brain injury: Effects of posttraumatic hypothermia.J Neurochem1995, 65:1704-1711.PubMedCrossRefGoogle Scholar
  180. 181.
    Globus MY, Busto R, Lin B, et al.: Detection of free radical activity during transient global ischemia and recirculation: Effects of intraischemic brain temperature modulation.J Neurochem1995, 65:1250-1256.PubMedCrossRefGoogle Scholar
  181. 182.
    Karibe H, Zarow GJ, Graham SH,et al.: Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats.J Cereb Blood Flow Metab1994, 14:620-627.PubMedCrossRefGoogle Scholar
  182. 183.
    Steinberg GK, Grant G, Yoon EJ: Deliberate hypothermia. InIntraoperative Neuroprotection. Edited by Andrews RJ. Philadelphia: Williams and Wilkins; 1996:65-84.Google Scholar
  183. 184.
    Spetzler RF, Hadley MN, Rigamonti D,et al.: Aneurysms of the basilar artery treated with circulatory arrest, hypothermia, and barbiturate cerebral protection.J Neurosurg1988, 68:868-879.PubMedCrossRefGoogle Scholar
  184. 185.
    Baker KZ, Young WL, Stone JG,et al.: Deliberate mild intraoperative hypothermia for craniotomy.Anesthesiology1994,81:361–367.PubMedCrossRefGoogle Scholar
  185. 186.
    Marion DW, Penrod LE, Kelsey SF,et al.: Treatment of traumatic brain injury with moderate hypothermia.N Engl J Med1997, 336:540–546.PubMedCrossRefGoogle Scholar
  186. 187.
    Shimizu T, Naritomi H, Kakuda W,et al.: Mild hypothermia is effective for the treatment of acute embolic stroke if induced within 24 hours after onset but not in the later phase.J Cereb Blood Flow Metab1997, 17:S42.Google Scholar
  187. 188.
    Suzuki T, Yoshimoto T: The effect of mannitol in prolongation of permissible occulsion time of cerebral arteries: Clinical data of aneurysm surgery. InCerebral Aneurysms. Edited by Suziki T. Tokyo: Neuron; 1979:330–337.Google Scholar
  188. 189.
    Meyer FB, Anderson RE, Sundt TM, Jr.,et al.: Treatment of experimental focal cerebral ischemia with mannitol: Assessment by intracellular brain pH, cortical blood flow, and electroencephalography.J Neurosurg1987, 66:109–115.PubMedCrossRefGoogle Scholar
  189. 190.
    Andrews RJ, Giffard RG: Clinically useful nonanesthetic agents for neuroprotection. InIntraoperative Neuroprotection. Edited by Andrews RJ. Philadelphia: Williams and Wilkins; 1996:37–63.Google Scholar
  190. 191.
    Batjer HH: Cerebral protective effects of etomidate: experimental and clinical aspects.Cerebrovasc Brain Metab Rev1993,5:17–32.PubMedGoogle Scholar
  191. 192.
    Chang SD, Lopez JR, Steinberg GK: Use of evoked potential monitoring in the intraoperative management of cerebral aneurysms [abstract].J Neurosurg1997, 86:400A.Google Scholar
  192. 193.
    Chang SD, Lopez JR, Steinberg GK: The use of electrophysiologic monitoring during resection of arteriovenous malformations and angiographically occult vascular malformations [abstract].Stroke1997,28:264.Google Scholar

Copyright information

© Current Medicine, Inc. 1998

Authors and Affiliations

  • Midori A Yenari
  • Gary K Steinberg

There are no affiliations available

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