Brain Protection

  • U. M. Illievich
  • A.-M. Machata
  • C. K. Spiss
Conference paper


The brain is critically dependent on a continuous supply of oxygen and glucose. Neuronal function depends almost exclusively on oxidative glucose metabolism and the brain has only limited stores of energy-generating substrates. Reduction of cerebral blood flow below a threshold required for maintaining the integrity compartment of the brain’s metabolism results in cerebral ischaemia, the major cause of metabolic brain injury. Cerebral ischaemia can be global or focal, which differ in cause, pathophysiology, localization, and to a certain extent in treatment strategies. Decreased global cerebral blood flow below ischaemic thresholds due to hypotension or insufficient cardiac output usually compromises the entire brain. In animal models of global cerebral ischaemia damage is most likely to occur first in certain vulnerable regions including the pyramidal cells of the CA1 region of the hippocampus (limbic system), Purkinje cells (cerebellum), and layers 3, 5, and 6 of the cortex. This pattern of selective vulnerable neurons has also been observed in humans, and may account for the poor neurologic outcome of survivors of cardiac arrest [1].


Traumatic Brain Injury Cerebral Blood Flow Severe Head Injury Mild Hypothermia Moderate Hypothermia 
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.
    Collins RC, Dobkin BH, Choi DW (1989) Selective vulnerability of the brain: new insights into the pathophysiology of stroke. Ann Intern Med 110:992–1000PubMedGoogle Scholar
  2. 2.
    Werner C, Möllenberg O, Kochs E, Schulte am Esch J (1995) Sevoflurane improves neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 75:756–760PubMedCrossRefGoogle Scholar
  3. 3.
    Engelhard K, Werner C, Reeker W, Lu H, Mollenberg O, Mielke L, Kochs E (1999) Desflurane and isoflurane improve neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 83:415–421PubMedCrossRefGoogle Scholar
  4. 4.
    Warner DS (1989) Volatile anesthetics and the ischemic brain. Journal of Neurosurgical Anesthesiology 1:290–294PubMedCrossRefGoogle Scholar
  5. 5.
    Spetzler RF, Martin N, Hadley MN, Thompson RA, Wilkinson E, Raudzens PA (1986) Microsurgical endarterectomy under barbiturate protection: a prospective study. J Neurosurg 65:63–73PubMedCrossRefGoogle Scholar
  6. 6.
    Belopavlovic M, Buchthal A (1980) Barbiturate therapy in the management of cerebral ischaemia. Anaesthesia 35:271–278PubMedCrossRefGoogle Scholar
  7. 7.
    Nussmeier NA, Arlund C, Slogoff S (1986) Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesthesiology 64:165–170PubMedCrossRefGoogle Scholar
  8. 8.
    Brain Resuscitation Clinical Trial I Study Group (1986): Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med 314:397–403CrossRefGoogle Scholar
  9. 9.
    Milde LN, Milde JH, Michenfelder JD (1985) Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs. Anesthesiology 63:371–377PubMedCrossRefGoogle Scholar
  10. 10.
    Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D (1984) Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 310:1415–1421PubMedCrossRefGoogle Scholar
  11. 11.
    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 76:807–812PubMedCrossRefGoogle Scholar
  12. 12.
    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 76:245–252PubMedCrossRefGoogle Scholar
  13. 13.
    Roach GW, Newman MF, Murkin JM, Martzke J, Ruskin A, Li J, Guo A, Wisniewski A, Mangano DT (1999) Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Anesthesiology 90:1255–1264PubMedCrossRefGoogle Scholar
  14. 14.
    Kelly DF, Goodale DB, Williams J, Herr DL, Chappell ET, Rosner MJ, Jacobson J, Levy ML, Croce MA, Maniker AH, Fulda GJ, Lovett JV, Mohan O, Narayan RK (1999) Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial. J Neurosurg 90:1042–1052PubMedCrossRefGoogle Scholar
  15. 15.
    Marcoux FW, Goodrich JE, Dominick MA (1988) Ketamine prevents ischemie neuronal injury. Brain Res 452:329–335PubMedCrossRefGoogle Scholar
  16. 16.
    Hoffman WE, Pelligrino D, Werner C, Kochs E, Albrecht RF, Schulte am Esch J (1992) Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats. Anesthesiology 76:755–762PubMedCrossRefGoogle Scholar
  17. 17.
    Wyte SR, Shapiro HM, Turner P, Harris AB (1972) Ketamine-induced intracranial hypertension. Anesthesiology 36:174–176PubMedCrossRefGoogle Scholar
  18. 18.
    Lanier WL, Stangland KJ, Scheithauer BW, Milde JH, Michenfelder JD (1987) The effects of dextrose infusion and head position on neurologic outcome after complete cerebral ischemia in primates: examination of a model. Anesthesiology 66:39–48PubMedCrossRefGoogle Scholar
  19. 19.
    Drummond JC, Moore SS (1989) The influence of dextrose administration on neurologic outcome after temporary spinal cord ischemia in the rabbit. Anesthesiology 70:64–70PubMedCrossRefGoogle Scholar
  20. 20.
    de Courten-Myers G, Myers RE, Schoolfield L (1988) Hyperglycemia enlarges infarct size in cerebrovascular occlusion in cats. Stroke 19:623–630PubMedCrossRefGoogle Scholar
  21. 21.
    Zasslow MA, Pearl RG, Shuer LM, Steinberg GK, Lieberson RE, Larson CP, Jr. (1989) Hyperglycemia decreases acute neuronal ischemic changes after middle cerebral artery occlusion in cats. Stroke 20:519–523PubMedCrossRefGoogle Scholar
  22. 22.
    Woo J, Lam CW, Kay R, Wong AH, Teoh R, Nicholls MG (1990) The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol 47:1174–1177PubMedCrossRefGoogle Scholar
  23. 23.
    Wood ER, Bussey TJ, Phillips AG (1993) A glycine antagonist 7-chlorokynurenic acid attenuates ischemia-induced learning deficits. Neuroreport 4:151–154PubMedCrossRefGoogle Scholar
  24. 24.
    Bacher A, Zornow MH (1997) Lamotrigine inhibits extracellular glutamate accumulation during transient global cerebral ischemia in rabbits. Anesthesiology 86:459–463PubMedCrossRefGoogle Scholar
  25. 25.
    Blair JL, Warner DS, Todd MM (1989) Effects of elevated plasma magnesium versus calcium on cerebral ischemic injury in rats. Stroke 20:507–512PubMedCrossRefGoogle Scholar
  26. 26.
    Newberg LA, Steen PA, Milde JH, Michenfelder JD (1984) Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia. Stroke 15:666–671PubMedCrossRefGoogle Scholar
  27. 27.
    Vaagenes P, Cantadore R, Safar P, Moossy J, Rao G, Diven W, Alexander H, Stezoski W (1984) Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs. Crit Care Med 12:846–855PubMedCrossRefGoogle Scholar
  28. 28.
    Milde LN, Milde JH, Michenfelder JD (1986) Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 6:332–337PubMedCrossRefGoogle Scholar
  29. 29.
    Paci A, Ottaviano P, Trenta A, Iannone G, De Santis L, Lancia G, Moschini E, Carosi M, Amigoni S, Caresia L (1989) Nimodipine in acute ischemie stroke: a double-blind controlled study. Acta Neurol Scand 80:282–286PubMedCrossRefGoogle Scholar
  30. 30.
    Zabramski J, Spetzler RF, Bonstelle C (1986) Chronic cerebral vasospasm: effect of calcium antagonists. Neurosurgery 18:129–135PubMedCrossRefGoogle Scholar
  31. 31.
    Robinson MJ, Teasdale GM (1990) Calcium antagonists in the management of subarachnoid haemorrhage. Cerebrovasc Brain Metab Rev 2:205–226PubMedGoogle Scholar
  32. 32.
    Barker FG, 2nd, Ogilvy CS (1996) Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg 84:405–414PubMedCrossRefGoogle Scholar
  33. 33.
    The European Study Group on Nimodipine in Severe Head Injury (1994) A multicenter trial of the efficacy of nimodipine on outcome after severe head injury. J Neurosurg 80:797–804CrossRefGoogle Scholar
  34. 34.
    Awad IA, Carter LP, Spetzler RF, Medina M, Williams FC, Jr. (1987) Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 18:365–372PubMedCrossRefGoogle Scholar
  35. 35.
    Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J et al ( 1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322:1405–1411PubMedCrossRefGoogle Scholar
  36. 36.
    Saul TG, Ducker TB, Salcman M, Carro E (1981) Steroids in severe head injury: A prospective randomized clinical trial. J Neurosurg 54:596–600PubMedCrossRefGoogle Scholar
  37. 37.
    Alderson P, Roberts I (1997) Corticosteroids in acute traumatic brain injury: systematic review of randomized controlled trials. BMJ 314:1855–1859PubMedCrossRefGoogle Scholar
  38. 38.
    Marshall LF, Maas AI, Marshall SB, Bricolo A, Fearnside M, Iannotti F, Klauber MR, Lagarrigue J, Lobato R, Persson L, Pickard JD, Piek J, Servadei F, Wellis GN, Morris GF, Means ED, Musch B (1998) A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury. J Neurosurg 89:519–525PubMedCrossRefGoogle Scholar
  39. 39.
    Kassell NF, Haley EC, Jr., Apperson-Hansen C, Alves WM (1996) 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 Neurosurg 84:221–228PubMedCrossRefGoogle Scholar
  40. 40.
    Yamamoto M, Shima T, Uozumi T, Sogabe T, Yamada K, Kawasaki T (1983) A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of alpha-tocopherol administration. Stroke 14:977–982PubMedCrossRefGoogle Scholar
  41. 41.
    Sakaki S, Ohta S, Nakamura H, Takeda S (1988) Free radical reaction and biological defense mechanism in the pathogenesis of prolonged vasospasm in experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 8:1–8PubMedCrossRefGoogle Scholar
  42. 42.
    Clifton GL, Lyeth BG, Jenkins LW, Taft WC, De Lorenzo RJ, Hayes RL (1989) Effect of D-alpha-tocopheryl succinate and polyethylene glycol on performance tests after fluid percussion brain injury. J Neurotrauma 6:71–81PubMedCrossRefGoogle Scholar
  43. 43.
    Liu TH, Beckman JS, Freeman BA, Hogan EL, Hsu CY (1989) Polyethylene glycol-conjugated Superoxide dismutase and catalase reduce ischemic brain injury. Am J Physiol 256:H589-593Google Scholar
  44. 44.
    Luvisotto TL, Auer RN, Sutherland GR (1996) The effect of mannitol on experimental cerebral ischemia, revisited. Neurosurgery 38:131–138; discussion 139PubMedCrossRefGoogle Scholar
  45. 45.
    Michenfelder JD, Theye RA ( 1970) The effects of anesthesia and hypothermia on canine cerebral ATP and lactate during anoxia produced by decapitation. Anesthesiology 33:430–439PubMedCrossRefGoogle Scholar
  46. 46.
    Minamisawa H, Nordstrom CH, Smith ML, Siesjo BK (1990) The influence of mild body and brain hypothermia on ischemic brain damage. J Cereb Blood Flow Metab 10:365–374PubMedCrossRefGoogle Scholar
  47. 47.
    Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD (1989) Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 20:904–910PubMedCrossRefGoogle Scholar
  48. 48.
    Illievich UM, Zornow MH, Choi KT, Serieller MS, Strnat MA (1994) Effects of hypothermic metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischemia. Anesth Analg 78:905–911PubMedCrossRefGoogle Scholar
  49. 49.
    Katsura K, Minamisawa H, Ekholm A, Folbergrova J, Siesjo BK (1992) Changes of labile metabolites during anoxia in moderately hypo-and hyperthermic rats: correlation to membrane fluxes of K+. Brain Res 590:6–12PubMedCrossRefGoogle Scholar
  50. 50.
    Widmann R, Miyazawa T, Hossmann KA ( 1993) Protective effect of hypothermia on hippocampal injury after 30 minutes of forebrain ischemia in rats is mediated by postischemic recovery of protein synthesis. J Neurochem 61:200–209PubMedCrossRefGoogle Scholar
  51. 51.
    Cardell M, Boris-Moller F, Wieloch T (1991) Hypothermia prevents the ischemia-induced translocation and inhibition of protein kinase C in the rat striatum. J Neurochem 57:1814–1817.PubMedCrossRefGoogle Scholar
  52. 52.
    Lei B, Tan X, Cai H, Xu Q, Guo Q (1994) Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation. Stroke 25:147–152PubMedCrossRefGoogle Scholar
  53. 53.
    Edwards AD, Yue X, Squier MV, Thoresen M, Cady EB, Penrice J, Cooper CE, Wyatt JS, Reynolds EO, Mehmet H (1995) Specific inhibition of apoptosis after cerebral hypoxiaischaemia by moderate post-insult hypothermia. Biochem Biophys Res Commun 217:1193–1199PubMedCrossRefGoogle Scholar
  54. 54.
    Jiang JY, Lyeth BG, Kapasi MZ, Jenkins LW, Povlishock JT (1992) Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat. Acta Neuropathol 84:495–500PubMedCrossRefGoogle Scholar
  55. 55.
    Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363–368PubMedCrossRefGoogle Scholar
  56. 56.
    Marion DW, Obrist WD, Carlier PM, Penrod LE, Darby JM (1993) The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg 79:354–362PubMedCrossRefGoogle Scholar
  57. 57.
    Marion DW, Penrod LE, Kelsey SF, Obrist WD, Kochanek PM, Palmer AM, Wisniewski SR, De Kosky ST (1997) Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med 336:540–546PubMedCrossRefGoogle Scholar
  58. 58.
    Clifton GL, Allen S, Barrodale P, Plenger P, Berry J, Koch S, Fletcher J, Hayes RL, Choi SC (1993) A phase II study of moderate hypothermia in severe brain injury. J Neurotrauma 10:263–271PubMedCrossRefGoogle Scholar
  59. 59.
    Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR, Jr., Muizelaar JP, Wagner FC, Jr., Marion DW, Luerssen TG, Chesnut RM, Schwartz M (2001) Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 344:556–563PubMedCrossRefGoogle Scholar
  60. 60.
    Hartung J, Cottrell JE (1998) Statistics and hypothermia. J Neurosurg Anesthesiol 10:1–4PubMedCrossRefGoogle Scholar
  61. 61.
    Craen RA, Gelb AW, Eliasziw M, Lok P (1994) Current anesthetic practices and use of brain protective therapies for cerebral aneurysm surgery at 41 North American Centers. J Neurosurg Anesthesiol 6:303Google Scholar
  62. 62.
    Hindman BJ, Todd MM, Gelb AW, Loftus CM, Craen RA, Schubert A, Mahla ME, Tomer JC (1999) Mild hypothermia as a protective therapy during intracranial aneurysm surgery: a randomized prospective pilot trial. Neurosurgery 44:23–32PubMedCrossRefGoogle Scholar
  63. 63.
    Bernard SA, Jones BM, Horne MK (1997) Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 30:146–153PubMedCrossRefGoogle Scholar
  64. 64.
    Holzer M, Behringer W, Schorkhuber W, Zeiner A, Sterz F, Laggner AN, Frass M, Siostrozonek P, Ratheiser K, Kaff A (1997) Mild hypothermia and outcome after CPR. Hypothermia for Cardiac Arrest (HACA) Study Group. Acta Anaesthesiol Scand Suppl 111:55–58PubMedGoogle Scholar
  65. 65.
    McGrath BJ, Guy J, Borel CO, Friedman AH, Warner DS (1995) Perioperative management of aneurysmal subarachnoid hemorrhage: Part 2. Postoperative management. Anesth Analg 81:1295–1302PubMedGoogle Scholar
  66. 66.
    Lee SH, Heros RC, Mullan JC, Korosue K (1994) Optimum degree of hemodilution for brain protection in a canine model of focal cerebral ischemia. J Neurosurg 80:469–475PubMedCrossRefGoogle Scholar
  67. 67.
    Tu YK, Heros RC, Candia G, Hyodo A, Lagree K, Callahan R, Zervas NT, Karacostas D (1988) Isovolemic hemodilution in experimental focal cerebral ischemia. Part 1: Effects on hemodynamics, hemorheology, and intracranial pressure. J Neurosurg 69:72–81PubMedCrossRefGoogle Scholar
  68. 68.
    Tu YK, Heros RC, Karacostas D, Liszczak T, Hyodo A, Candia G, Zervas NT, Lagree K (1988) Isovolemic hemodilution in experimental focal cerebral ischemia. Part 2: Effects on regional cerebral blood flow and size of infarction. J Neurosurg 69:82–91PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2002

Authors and Affiliations

  • U. M. Illievich
    • 1
  • A.-M. Machata
    • 1
  • C. K. Spiss
    • 1
  1. 1.Department of Anaesthesiology and General Intensive CareUniversity of ViennaViennaAustria

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