Brain Ischemia and Reperfusion Injury

  • J. R. Kirsch
  • M. A. Helfaer
  • R. C. Koehler
  • R. J. Traystman
Conference paper
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 9)

Abstract

During ischemia, brain injury results from an inadequate supply of substrate (oxygen and glucose) to meet metabolic needs. The most common clinical etiology for cerebral hypoxia is cerebral ischemia or the lack of an adequate blood supply to meet the brain’s metabolic needs. Cerebral ischemia may occur in a variety of clinical settings including head trauma, postsurgical brain swelling, subarachnoid hemorrhage, stroke, and cardiac arrest. Even though ischemia is a recurring theme in each of these clinical settings it is clear from laboratory work that the pathophysiology of brain injury varies with different types of ischemia and therefore requires different therapeutic interventions. We will begin this review with a discussion of blood flow and metabolic changes during ischemia and the role of ion fluxes, ischemia induced release of excitatory amino acids and production of oxygen-derived free radicals in the pathophysiology of ischemic brain injury. We will conclude with a discussion of potential therapeutic options in protecting the brain from ischemic damage.

Keywords

Morphine Adenosine Prostaglandin Epinephrine Mannitol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ljunggren B, Ratcheson RA, Siesjö BK (1974) Cerebral metabolic state following complete compression ischemia. Brain Res 73:291–307PubMedCrossRefGoogle Scholar
  2. 2.
    Little JR, Kerr FWL, Sundt TM Jr (1975) Microcirculatory obstruction in focal cerebral ischemia: relationship to neuronal alterations. Mayo Clin Proc 50:264–270PubMedGoogle Scholar
  3. 3.
    Kalimo H, Rehncrona S, Sonderfedt B, Olsson Y, Siesjö BK (1981) Brain lactic acidosis and ischemic cell damage: II. Histopathology. J Cereb Blood Flow Metab 1:313–327PubMedCrossRefGoogle Scholar
  4. 4.
    Siesjö BK (1984) Cerebral circulation and metabolism. J Neurosurg 60:883–908PubMedCrossRefGoogle Scholar
  5. 5.
    Bazan NG Jr, DeBazan HEP, Kennedy WG, et al (1971) Regional distribution and rate of production of free fatty acids in rat brain. J Neurochem 18:1387–1393PubMedCrossRefGoogle Scholar
  6. 6.
    Kontos HA, Wei EP, Povlishock JT, Christman CW (1984) Oxygen radicals mediate the cerebral arteriolar dilation form arachidonate and bradykinin in cats. Circ Res 55:295–303PubMedGoogle Scholar
  7. 7.
    Wei EP, Christman CW, Kontos HA, et al (1985) Effects of oxygen radicals on cerebral arterioles. Am J Physiol 248:H157–H162PubMedGoogle Scholar
  8. 8.
    Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374PubMedCrossRefGoogle Scholar
  9. 9.
    Greenamyre JT, Young AB, Penney JB (1984) Quantitative autoradiographic distribution of L-[3H]glutamate binding sites in rat central nervous system. J Neurosci 4:2133–2144PubMedGoogle Scholar
  10. 10.
    Curtis DR, Phillis JW, Watkins JC (1959) Chemical excitation of spinal neurones. Nature 183:611–612PubMedCrossRefGoogle Scholar
  11. 11.
    Farber JL, Chien KR, Mittnachts (1981) The pathogenesis of irreversible cell injury in ischemia. Am J Physiol 102:271–281Google Scholar
  12. 12.
    Drejer J, Benveniste H, Diemer MH, Schousboe A (1985) Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45:145–151PubMedCrossRefGoogle Scholar
  13. 13.
    Van Wylen DGL, Park TS, Rubio R, Berne RM (1986) Increases in cerebral interstitial fluid adenosine concentration during hypoxia, local potassium infusion, and ischemia. J Cereb Blood Flow Metab 6:522–528PubMedCrossRefGoogle Scholar
  14. 14.
    Al-Khalidi UAS, Chaglassian TH (1965) The specific distribution of xanthine oxidase. Biochem J 97:318–320PubMedGoogle Scholar
  15. 15.
    Betz AL (1985) Identification of hypoxanthine transport and xanthine oxidase activity in brain capillaries. J Neurochem 44:574–579PubMedCrossRefGoogle Scholar
  16. 16.
    Beckman JS, Campbell GA, Freeman BA (1986) Conversion of brain xanthine dehydrogenase to oxidase contributes to cerebral ischemic injury in the gerbil. Free radicals in biology and medicine: Ischemia/Reperfusion injury. Presented at the Grand Hotel Point Clear, Alabama, March 17–19Google Scholar
  17. 17.
    Hosobuchi Y, Basins DS, Woo SK (1982) Reversal of induced ischemic neurologic deficit in gerbils by the opiate antagonist naloxone. Science 215:69–71PubMedCrossRefGoogle Scholar
  18. 18.
    Sandor P, Gotoh F, Tomita M, Tanahashi M, Gogolak I (1986) Effects of a stable enke-phalin analogue, (D-Met2, Pro5)-enkephalinamide, and naloxone on cortical blood flow and cerebral blood volume in experimental brain ischemia in anesthetized cats. Cereb Blood Flow Metab 6:553–558CrossRefGoogle Scholar
  19. 19.
    Hall ED, Pazara KE (1988) Quantitative analysis of effects of k-opioid agonists on postis-chemic hippocampal CA1 neuronal necrosis in gerbils. Stroke 19:1008–1012PubMedCrossRefGoogle Scholar
  20. 20.
    Longstreth WT, Invi TS, Cobb LA, Copass MK (1983) Neurologic recovery after out-of-hospital cardiac arrest. Ann Intern Med 98:588–592PubMedGoogle Scholar
  21. 21.
    Bircher N, Safar P (1985) Cerebral preservation during cardiopulmonary resuscitation. Crit Care Med 13:185–190PubMedCrossRefGoogle Scholar
  22. 22.
    Michael R, Guerci AD, Koehler RC, et al (1984) Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs. Circulation 69:822–835PubMedCrossRefGoogle Scholar
  23. 23.
    Arai T, Dote K, Tsuahara I, Nitta K, Nagaro T (1984) Cerebral blood flow during conventional, new and open-chest cardiopulmonary resuscitation in dogs. Resuscitation 12:147–154PubMedCrossRefGoogle Scholar
  24. 24.
    Shiu GK, Nemoto EM (1981) Barbiturate attenuation of brain free fatty acid liberation during global ischemia. Neurochem 37:1448–1456CrossRefGoogle Scholar
  25. 25.
    Dorman RV (1988) Effects of cerebral ischemia and reperfusion on prostanoid accumulation in unanesthetized and pentobarbital-anesthetized gerbils. J Cereb Blood Flow Metab 8:609–612PubMedCrossRefGoogle Scholar
  26. 26.
    Smith DS, Rehncrona S, Siesjö BK (1980) Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro. Acta Physiol Scand 42:129–134Google Scholar
  27. 27.
    Godin DV, Mitchell J, Saunders BA (1982) Studies on the interaction of barbiturates with reactive oxygen radicals: implications regarding barbiturate protection against cerebral ischemia. Can Anaesth Soc J 29:203–210PubMedCrossRefGoogle Scholar
  28. 28.
    Goldstein A Jr, Wells BA, Keats AS (1966) Increased tolerance to cerebral anoxia by pen-tobarbital. Arch Int Pharmacodyn Ther 161:138–143PubMedGoogle Scholar
  29. 29.
    Todd MM, Chadwick HS, Shapiro HM, Dunlop BS, Marshall LF, Dueck R (1982) The neurologic effects of thiopental therapy following experimental cardiac arrest in cats. Anesthesiology 57:76–86PubMedCrossRefGoogle Scholar
  30. 30.
    Abramson NS, Safar P, Detre KM, et al (1986) Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med 314:397–403CrossRefGoogle Scholar
  31. 31.
    Smith AL, Hoff T, Nielsen SL, et al (1974) Barbiturate protection in acute focal cerebral ischemia. Stroke 5:1–7PubMedCrossRefGoogle Scholar
  32. 32.
    Meyer FB, Sundt TM, Yanagihara, Anderson RE (1987) Focal cerebral ischemia: Patho-physiologic mechanism and rationale for future avenues of treatment. Mayo Clin Proc 62:35–55PubMedGoogle Scholar
  33. 33.
    Meyer FB, Anderson RE, Yaksh TL, et al (1986) Effect of nimodipine on intracellular NV brain pH, cortical blood flow, and EEG in experimental focal cerebral ischemia. J Neurosurg 64:617–626PubMedCrossRefGoogle Scholar
  34. 34.
    Weir B, Grace M, Hansen J, et al (1978) Time course of vasospasm in man. J Neurosurg 48:173–178PubMedCrossRefGoogle Scholar
  35. 35.
    Leblanc R, Feindel W, Yamamoto L, Milton JG, Frojmovic MM (1984) Reversal of acute experimental cerebral vasospasm by calcium antagonism with verapamil. Can J Neurol Sci 11:42–47PubMedGoogle Scholar
  36. 36.
    Guggiari M, Taquoi G, Philippon J, et al (1987) Curative treatment with intravenous nimodipine for cerebral vasospasm after subarachnoid haemorrhage due to aneurysm rupture. Anesthesiology (abstr) 67:A584CrossRefGoogle Scholar
  37. 37.
    Steen PA, Newberg LA, Milde H, et al (1983) Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. Cereb Blood Flow Metab 3:38–43CrossRefGoogle Scholar
  38. 38.
    Steen PA, Newberg LA, Milde H, et al (1984) Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 4:82–87PubMedCrossRefGoogle Scholar
  39. 39.
    White BC, Gadzinski DS, Hoehner P, et al (1982) Effect of flunarizine on canine cerebral cortical blood flow and vascular resistance post cardiac arrest. Ann Emerg Med 111:119–126CrossRefGoogle Scholar
  40. 40.
    Newberg LA, Steen PA, Milde JH, et al (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
  41. 41.
    Shapiro HM (1985) Postcardiac arrest therapy. Calcium entry blockade and brain resuscitation. Anesthesiology 62:384–387PubMedCrossRefGoogle Scholar
  42. 42.
    French LA, Galicich JH (1964) The use of steroids for control of cerebral edema. Clin Neurosurg 10:212PubMedGoogle Scholar
  43. 43.
    Siegel BA, Studer RK, Potchen E (1972) Sterioid therapy of brain edema: ineffectiveness in experimental cerebral microembolism. Arch Neurol 27:209–212PubMedCrossRefGoogle Scholar
  44. 44.
    Gaudet RJ, Levine L (1979) Transient cerebral ischemia and brain prostaglandins. Biochem Biophys Res Commun 86:893–901PubMedCrossRefGoogle Scholar
  45. 45.
    Furlow TW, Hallenbeck JM (1978) Indomethacin prevents impaired perfusion of the dog’s brain after global ischemia. Stroke 9:591–594PubMedCrossRefGoogle Scholar
  46. 46.
    Hallenbeck JM, Furlow TW (1979) Prostaglandin 12 and indomethacin prevent impairment of post-ischemic brain reperfusion in the dog. Stroke 10:629–637PubMedCrossRefGoogle Scholar
  47. 47.
    Boulu RG, Plotine M, Gueniau C, Sofeir M, Wiernspeger N (1982) Effect of indomethacin in experimental cerebral ischemia. Pathol Biol 30:278–281PubMedGoogle Scholar
  48. 48.
    Gryglewski RJ, Nowak S, Kostka-Trabka E, et al (1983) Treatment of ischemic stroke with prostacyclin. Stroke 14:197–202PubMedCrossRefGoogle Scholar
  49. 49.
    Itoh T, Kawakami M, Yamauchi Y, et al (1986) Effect of allopurinol on ischemia and reperfusion-induced cerebral injury in spontaneously hypertensive rats. Stroke 17:1284–1287PubMedCrossRefGoogle Scholar
  50. 50.
    Martz D, Rayos G, Schielke GP, et al (1988) Allopurinol limits infarct size in partial ischemia. The seventh international symposium on intracranial pressure and brain injury, June 19–23, Ann Arbor, Michigan USA, p 33Google Scholar
  51. 51.
    Lim KH, Connolly M, Rose D, et al (1986) Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant Superoxide dismutase. Ann Thorac Surg 42:282–286PubMedCrossRefGoogle Scholar
  52. 52.
    Linsay SL, Beckman JS, Liu TH, et al (1988) The effect of Superoxide dismutase and catalase on focal cerebral ischemia. Anesthesiology A215Google Scholar
  53. 53.
    Fleischer JE, Lanier WL, Milde JH, et al (1987) Failure of deferoxamine, an iron chelator, to improve neurologic outcome following complete cerebral ischemia in dogs. Stroke 18:124–127PubMedCrossRefGoogle Scholar
  54. 54.
    Coles JC, Ahmed SN, Mehta HU, et al (1986) Role of free radical scavenger in protection of spinal cord during ischemia. Ann Thorac Surg 41:551–556PubMedCrossRefGoogle Scholar
  55. 55.
    McGraw CP (1983) Treatment of cerebral infarction with dimethyl sulfoxide in the Mongolian gerbil. Ann NY Acad Sci 411:278–285PubMedCrossRefGoogle Scholar
  56. 56.
    Little JR (1979) Treatment of acute focal cerebral ischemia with intermittent, low dose mannitol. Neurosurgery 5:687–691PubMedCrossRefGoogle Scholar
  57. 57.
    Simon RP, Swan JH, Griffiths T, Meldrum BS (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226:850–852PubMedCrossRefGoogle Scholar
  58. 58.
    Izumiyama K, Kogure K (1988) Prevention of delayed neuronal death in gerbil hippocampus by ion channel blockers. Stroke 19:1003–1007PubMedCrossRefGoogle Scholar
  59. 59.
    Mullie A, Hermans C, Vandevelde K, et al (1981) Resuscitability of the heart with brain protective drugs during cardiopulmonary resuscitation in dogs. Crit Care Med 9:183CrossRefGoogle Scholar
  60. 60.
    Hempelmann G, Dieter K, Volker L, et al (1982) Cerebral protection in neurosurgery, cardiac surgery, and following cardiac arrest. J Cereb Blood Flow Metab 2:S66–S71PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • J. R. Kirsch
  • M. A. Helfaer
  • R. C. Koehler
  • R. J. Traystman

There are no affiliations available

Personalised recommendations