Progression and Irreversibility in Brain Ischaemia

  • Lindsay Symon
Part of the NATO ASI Series book series (NSSA, volume 115)


In recent years the twin concepts of thresholds of ischaemia and of the ischaemic penumbra have proved useful hypotheses in the investigation and management of cerebrovascular disease. This paper presents the current status of these concepts. The notion of an ischaemic threshold arose from clinical observation. It has long been clear in clinical neurosurgery, for example, that patients recovering from anaesthesia may show the progressive clearance of a neurological deficit, that some patients who develop a neurological deficit with lower blood pressure have that deficit promptly cleared when blood pressure is elevated and that patients with established cerebrovascular occlusion and dense neurological deficits may show quite evident improvement over months or years. While in this last example some of the potential for re-learned circuitry in the nervous system may play a part, it is clear that in more acute circumstances neurons which at one time are non-functioning, may under improved conditions of perfusion return to normal function.


Cerebral Blood Flow Middle Cerebral Artery Middle Cerebral Artery Occlusion Spreading Depression Brain Water Content 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Collewijn H, and Van Harreveld A, Membrane potential of cerebral cortical cells during spreading depression and asphyxia, Exp Neurol 15: 425 (1966).CrossRefGoogle Scholar
  2. 2.
    Collewijn H, and Van Harreveld A, Intracellular recording of spinal motoneurones during acute asphyxia, J Physiol 185: 1 (1966).Google Scholar
  3. 3.
    Van Harreveld A, and Tachibana S, Recovery of cerebral cortex from asphyxiation, Amer J Physiol 202: 59 (1962).Google Scholar
  4. 4.
    Hossmann KA, Cortical steady potential, impedance and excitability changes during and after total ischemia of cat brain, Exp Neurol 32: 163 (1971).CrossRefGoogle Scholar
  5. 5.
    Brierley JB, Salford LG, Siesjö BK, and Plum F, Moderate hypoxic ischemia irreversibly damages rat brain in 30 minutes, Stroke 4: 339 (1973).Google Scholar
  6. 6.
    Grossman RG, Turner JW, Miller JD, and Rowan JO, The relationship between cortical electrical activity, cerebral perfusion pressure and cerebral blood flow during increased intracranial pressure, Stroke 4: 346 (1973).Google Scholar
  7. 7.
    Ingvar DH, Normal and postanoxic regulation of the regional cerebral blood flow, in: “Recent advances in the study of cerebral circulation”, Taveras et al., eds., Thomas, Springfield, Illinois (1970).Google Scholar
  8. 8.
    Boysen G, Engell HC, and Trojaborg W, Effect of mechanical rCBF reduction on EEG in man, Stroke 4: 361 (1973).Google Scholar
  9. 9.
    Meyer JS, and Marx P, The pathogenesis of EEG changes during cerebral anoxia, in: “Handbook of EEG and clinical neurophysiology”, Remond A, ed., Elsevier, Amsterdam (1972).Google Scholar
  10. 10.
    Hossmann KA, and Sato K, Effect of ischemia on the function of the sensorimotor cortex in cat, Electroenceph Clin Neurophysiol 30: 535 (1971).CrossRefGoogle Scholar
  11. 11.
    Przybylski A, Activity pattern of visceral cortex neurons during asphyxia, Exp Neurol 32: 12 (1971).CrossRefGoogle Scholar
  12. 12.
    Harvey J, and Rasmussen T, Occlusion of the middle cerebral artery, Arch Neurol 66: 20 (1951).Google Scholar
  13. 13.
    Symon L, Studies of leptomeningeal collateral circulation in macacus rhesus, J Physiol 159: 68 (1961).Google Scholar
  14. 14.
    Symon L, Dorsch NWC, and Ganz JC, Lactic acid efflux from ischaemic brain, J Neurol Sci 17: 411 (1972).CrossRefGoogle Scholar
  15. 15.
    Yamaguchi T, Waltz AG, and Okazaki H, Hyperemia and ischemia in experimental cerebral infarction: Correlation of histopathology and regional blood flow, Neurology 21: 565 (1971).CrossRefGoogle Scholar
  16. 16.
    Symon L, Pasztor E, and Branston NM, The distribution and density of reduced cerebral blood flow following acute middle cerebral artery occlusion: An experimental study by the technique of hydrogen clearance in baboons, Stroke 5: 355 (1974).CrossRefGoogle Scholar
  17. 17.
    Kaplan HA, and Ford DH, “The brain vascular system”, Elsevier, London (1966).Google Scholar
  18. 18.
    Lazorthes G, and Campan L, “La cirulation cerebrale”, Editions Sandoz, Paris (1964).Google Scholar
  19. 19.
    Pasztor E, Symon L, Dorsch NWC, and Branston NM, The hydrogen clearance method in assessment of blood flow in cortex, white matter and deep nuclei of baboons, Stroke 4: 556 (1973).CrossRefGoogle Scholar
  20. 20.
    Heiss WD, Hayakawa T, and Waltz AG, Cortical neuronal function during ischemia - Effects of occlusion of one middle cerebral artery on single-unit activity in cats, Arch Neurol 33: 813 (1976).CrossRefGoogle Scholar
  21. 21.
    Trojaborg W, and Boysen G, Relation between EEG, regional cerebral blood flow and internal carotid artery pressure during carotid endarterectomy, Electroenceph Clin Neurophysiol 34: 61 (1973).CrossRefGoogle Scholar
  22. 22.
    Gregory PC, McGeorge AP, Fitch W, Graham DI, Mackenzie ET, and Harper AM, Effects of hemorrhagic hypotension on cerebral circulation. II. Electrocortical function, Stroke 10: 719 (1979).CrossRefGoogle Scholar
  23. 23.
    Branston NM, Symon L, Crockard HA, Pasztor E, Relationship between the cortical evoked potential and local cortical blood flow following acute middle cerebral artery occlusion in the baboon, Exp Neurol 45: 195 (1974).CrossRefGoogle Scholar
  24. 24.
    Marshall LF, Welsh F, Durity F, Lounsbury R, Graham DI, and Langfitt TW, Experimental cerebral oligemia and ischemia produced by intracranial hypertension. Part 3: Brain energy metabolism, J Neurosurg 43: 323 (1975).CrossRefGoogle Scholar
  25. 25.
    Astrup J, Symon L, Branston NM, and Lassen NA, Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia, Stroke 8: 51 (1977).CrossRefGoogle Scholar
  26. 26.
    Astrup J, Blennow G, and Nilsson B, Effects of reduced cerebral blood flow on EEG pattern, cerebral extracellular potassium, and energy metabolism in the rat cortex during bicuculline-induced seizure, Brain Res 177: 115 (1979).CrossRefGoogle Scholar
  27. 27.
    Zimmerman ANE, and Hulsman WC, Paradoxical influence of calcium ions on the permeability of the cell membranes of the isolated rat heart, Nature 211: 646 (1966).CrossRefGoogle Scholar
  28. 28.
    Shen AC, and Jennings RB, Myocardial calcium and magnesium in acute ischemic injury, Am J Pathol 67: 417 (1972).Google Scholar
  29. 29.
    Shen AC, and Jennings RB, Kinetics of calcium accumulation in acute myocardial ischemic injury, Am J Pathol 67: 441 (1972).Google Scholar
  30. 30.
    Hearse DJ, Reperfusion of the ischemic myocardium, J Mol Cell Cardiol 9: 605 (1977).CrossRefGoogle Scholar
  31. 31.
    Kraig RP, and Nicholson C, Extracellular ionic variations during spreading depression, Neurosciences 3: 1045 (1978).CrossRefGoogle Scholar
  32. 32.
    Nicholson C, Dynamics of the brain cell microenvironment, Neurosci Res Prog Bull 18: 177 (1980).Google Scholar
  33. 33.
    Van Breemen C, Calcium requirement for activation of intact aortic smooth muscle, J Physiol 272: 317 (1977).Google Scholar
  34. 34.
    Baker PF, Hodgkin AL, and Ridgway EB, Depolarization and calcium entry in squid giant axons, J Physiol 218: 709 (1971).Google Scholar
  35. 35.
    Katz B, and Miledi R, Further study of the role of calcium in synaptic transmission, J Physiol 207: 789 (1970).Google Scholar
  36. 36.
    Branston NM, Strong AJ, and Symon L, Extracellular potassium activity, evoked potential and tissue blood flow, relationship during progressive ischaemia in baboon cerebral cortex, J Neurol Sci 32: 305 (1977).CrossRefGoogle Scholar
  37. 37.
    Harris RJ, Symon L, Branston NM, and Bayhan M, Changes in extra-cellular calcium activity in cerebral ischaemia, J Cereb Blood Flow Metabol 1: 203 (1981).CrossRefGoogle Scholar
  38. 38.
    Hossmann KA, Sakaki S, and Zimmermann V, Cation activities in reversible ischaemia of the cat brain, Stroke 8: 77 (1977).CrossRefGoogle Scholar
  39. 39.
    Adey WR, Evidence for cerebral membrane effects of calcium derived from current gradient impedance and intracellular records, Exp Neurol 30: 78 (1971).CrossRefGoogle Scholar
  40. 40.
    Branston NM, Strong AJ, and Symon L, Impedance related to local blood flow in cerebral cortex, J Physiol 275: 81P (1978).Google Scholar
  41. 41.
    Hansen AJ, and Olsen CE, Brain extracellular space during spreading depression and ischaemia, Acta Physiol Scand 108: 355 (1981).CrossRefGoogle Scholar
  42. 42.
    Hass WK, Beyond cerebral blood flow, metabolism and ischaemic thresholds: an examination of the role of calcium in the initiation of cerebral infarction, in: “Cerebral vascular disease 3”, Meyer JS et al., eds., Excerpta Medica, Amsterdam (1981).Google Scholar
  43. 43.
    Schanne FAX, Kane AB, Young EE, and Farber JL, Calcium dependence of toxic cell death: A final common pathway, Science 206: 700 (1979).CrossRefGoogle Scholar
  44. 44.
    Brierley JB, and Symon L, The extent of infarcts in baboon brain three years after division of the middle cerebral artery, J Neuropath Appl Neurobiol 3: 217 (1977).Google Scholar
  45. 45.
    Morawetz RB, De Girolami U, Ojemann RG, Marcoux FW, and Crowell RM, Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanaesthetized monkeys, Stroke 9: 143 (1978).CrossRefGoogle Scholar
  46. 46.
    Walker JL, Specific liquid ion exchanger micro electrodes, Analytical Chemistry 43: 83a (1971).Google Scholar
  47. 47.
    Bowen MD, Goodhard NJ, Strong AJ, Smith SM, White B, Branston NM, Symon L, and Davison AN, Biochemical indices of brain structure, function, and hypoxia in cortex from baboons with middle cerebral artery occlusion, Brain Research 177: 503 (1976).CrossRefGoogle Scholar
  48. 48.
    Symon L, Branston NM, and Chikovani O, Ischaemic brain oedema following middle cerebral artery occlusion in baboons. Relationship between regional cerebral water content and blood flow at 1–2 hours, Stroke 10: 184 (1979).CrossRefGoogle Scholar
  49. 49.
    Hossmann KA, and Schuier FJ, The metabolic (cytotoxic) type of brain oedema following middle cerebral artery occlusion in cats, in: “Cerebrovascular diseases”, Price T, Nelson E, eds., Raven, New York (1979).Google Scholar
  50. 50.
    O’Brien MD, Waltz AG, and Jordan NM, Ischaemic cerebral oedema. Distribution of water in brains of cats after occlusion of the middle cerebral artery, Arch Neurol 30: 456 (1974).Google Scholar
  51. 51.
    Hossmann KA, and Takagi S, Osmolality of brain in cerebral ischaemia, Exp Neurol 51: 124 (1976).Google Scholar
  52. 52.
    Sharbrough FW, Messick JM, and Sundt TM, Correlation of continuous electroencephalograms with cerebral blood flow measurements during carotid endarterectomy, Stroke 4: 674 (1973).Google Scholar
  53. 53.
    Trojaborg W, and Boysen G, Relation between EEG, regional cerebral blood flow and internal carotid artery pressure during carotid endarterectomy, Electroenceph Clin Neurophysiol 34: 61 (1973).Google Scholar
  54. 54.
    Heiss WD, Waltz AG, and Hayakawa T, Neuronal function and local blood flow during experimental cerebral ischaemia, in: “Blood flow and metabolism in the brain”, Harper AM, Jennett WB, Miller JD, Rowan JO, eds., Churchill Livingstone, London (1975).Google Scholar
  55. 55.
    Lassen NA, The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localized within the brain, Lancet 2: 113 (1966).Google Scholar
  56. 56.
    Zwetnow NN, Effects of increased cerebrospinal fluid pressure on the blood flow and on the energy metabolism of the brain, Acta Physiol Scand Suppl 339: 1 (1970).Google Scholar
  57. 57.
    Symon L, Ganz JC, and Dorsch NWC, Experimental studies of hyperaemic phenomena in the cerebral circulation of primates, Brain 95: 265 (1972).CrossRefGoogle Scholar
  58. 58.
    Waltz AG, Red venous blood: Occurrence and significance in ischemic and non-ischemic cerebral cortex, J Neurosurg 31: 141 (1969).CrossRefGoogle Scholar
  59. 59.
    Harvey J, and Rasmussen T, Occlusion of the middle cerebral artery: An experimental study, Arch Neurol Psychiat 66: 20 (1951).Google Scholar
  60. 60.
    Symon L, Hargadine J, Zawarski M, and Branston NM, Central conduction time as an index of ischaemia in subarachnoid haemorrhage, J Neurol Sci 44: 95 (1979).CrossRefGoogle Scholar
  61. 61.
    Wang AD, Cone J, Symon L, and Costa de Silva IE, Somatosensory evoked potential monitoring during the management of aneurysmal subarachnoid haemorrhage, J Neurosurg 60: 264 (1984)CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Lindsay Symon
    • 1
  1. 1.Institute of NeurologyGough Cooper Department of Neurological SurgeryLondonUK

Personalised recommendations