Skip to main content
SpringerLink
Log in

The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

The neuronal response to complete cerebral ischemia (CCI) of 5–15 min duration was evaluated at the light and electron microscopic level subsequent to postischemic recirculation periods of up to 60 min. Following postischemic reperfusion, the homogeneous neuronal changes characteristic of permanent CCI were modified into a heterogeneous pattern of selectively vulnerable neuronal responses. Four basic types of neuronal injury were represented within this heterogeneous neuronal population. The Type I neuronal response was most numerous and consisted of chromatin clumping, nucleolar condensation and a breakdown of polysomes. This response may represent a reversal of some of the neuronal changes observed after permanent CCI. In addition to the above changes, Type II neurons contained swollen mitochondria and Golgi saccules which appeared as microvacuoles under the light microscope. Type III neurons displayed varying degrees of neuronal shrinkage and numerous swollen mitochondria. Type IV neurons were markedly shrunken and electron-dense with few identifiable subcellular structures. The distribution of Type I neurons was random but the other neuronal responses occurred in “selectively vulnerable” brain regions. The number of Type II, III, and IV neurons increased with extended insult durations but were unaffected by the length of recirculation. Ten minutes of CCI represented the threshold for a significant increase in the number of severely altered neurons. These findings suggest that considerable neuronal injury may be present after 10–15 min of CCI, and the lack of a recirculation period following CCI appears to afford the brain parenchyma an extensive degree of structural protection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ames A III, Wright RL, Kowada M, Thurston JM, Majno G (1968) Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol 52:437–453

    Google Scholar 

  2. Arsenio-Nunes ML, Hossmann K-A, Farkas Bargeton E (1973) Ultrastructural and histochemical investigation of the cerebral cortex of cat during and after complete ischemia. Acta Neuropathol (Berl) 26:329–344

    Google Scholar 

  3. Bleyaert AL, Nemoto EM, Safar P (1978) Thiopental amelioration of brain damage after global ischemia in monkeys. Anesthesiology 49:390–398

    Google Scholar 

  4. Bourke RS, Kimelberg HK, Nelson LR, Barron KD, Auen EL, Popp AJ, Waldman JB (1980) Biology of glial swelling in experimental brain edema. In: Cervos-Navarro J, Ferszt R (eds) Brain edema. Adv Neurol 28:99–109

    Google Scholar 

  5. Brierley JB, Meldrum BS, Brown AW (1973) The threshold and neuropathology of cerebral “anoxic-ischemic” cell change. Arch Neurol 29:367–374

    Google Scholar 

  6. Brierley JB, Ljunggren B, Siesjo BK (1974) Neuropathological alterations in rat brain after complete ischaemia due to raised intracranial pressure. In: Lundberg N, Ponten U, Brock M (eds) Intracranial pressure II. Springer, Berlin Heidelberg New York, pp 166–171

    Google Scholar 

  7. Brierly JB (1976) Cerebral hypoxia. In: Blackwood W, Corsellis JAN (eds) Greenfield's neuropathology. Arnold, London, pp 43–85

    Google Scholar 

  8. Cammermeyer J (1978) Is the solitary dark neuron a manifestation of postmortem trauma to the brain inadequately fixed by perfusion? Histochemistry 56:97–115

    Google Scholar 

  9. Chiang J, Kowada M, Ames A, Wright R, Majno G (1968) Cerebral ischemia III. Vascular changes. Am J Pathol 52:455–476

    Google Scholar 

  10. Dampney RAL, Kumada M, Reis DJ (1979) Central neural mechanisms of the cerebral ischemic response: I. Characterization, effect of brainstem and cranial nerve transections, and simulation by electrical stimulation of restricted regions of medulla oblongata in rabbit. Circ Res 44:48–62

    Google Scholar 

  11. Demopoulos HB (1973) The basis of free radical pathology. Fed Proc 32:1859–1861

    Google Scholar 

  12. Demopoulos HB (1973) Control of free radicals in biologic systems. Fed Proc 32:1903–1908

    Google Scholar 

  13. Ellis EF, Wei EP, Kontos HA (1979) Vasodilation of cat cerebral arterioles by prostaglandins D2, E2, G2 and I2. Am J Physiol 237:381–385

    Google Scholar 

  14. Flamm ES, Demopoulos HB, Seligman ML, Poser RG, Ransohoff J (1978) Free radicals in cerebral ischemia. Stroke 9:445–447

    Google Scholar 

  15. Fischer EG, (1973) Impaired perfusion following cerebrovascular stasis: A review. Arch Neurol 29:361–366

    Google Scholar 

  16. Fischer EG, Ames A III, Hedley-Whyle ET, O'Gorman S (1977) Reassessment of cerebral capillary changes in acute global ischemia and their relationship to the “no-reflow phenomenon”. Stroke 8:36–39

    Google Scholar 

  17. Fischer EG, Ames A III, Lorenzo AV (1979) Cerebral blood flow immediately following brief circulatory stasis. Stroke 10:423–427

    Google Scholar 

  18. Frank JS, Beydler S, Kreman M, Rau EE (1980) Structure of the freeze-fractured sarcolemma in the normal and anoxic rabbit myocardium. Circ Res 47:131–143

    Google Scholar 

  19. Fridovich I (1979) Hypoxia and oxygen toxicity. In: Fahn S, Davis JN, Rowland LP (eds) Cerebral hypoxia and its consequences. Adv Neurol 26:255–266

  20. Furlow TW, Hallenbeck JM (1978) Indomethacin prevents impaired perfusion of the dog's brain after global ischemia. Stroke 9:591–594

    Google Scholar 

  21. Garcia JH, Lossinsky AS, Kauffman FC, Conger KA (1978) Neuronal ischemic injury: Light microscopy, ultrastructure, and biochemistry. Acta Neuropathol (Berl) 43:85–95

    Google Scholar 

  22. Gaudet RJ, Levine L (1979) Transient cerebral ischemia and brain prostaglandins. Biochem Biophys Res Commun 86:893–901

    Google Scholar 

  23. Gauder RJ, Alan I, Levine L (1980) Accumulation of arachidonic acid metabolites in gerbil brain during reperfusion after bilateral carotid artery occlusion. J Neurochem 35:653–658

    Google Scholar 

  24. Ginsberg MD, Myers RE (1972) The topography of impaired microvascular perfusion in the primate brain following total circulatory arrest. Neurology 27:998–1011

    Google Scholar 

  25. Ginsberg MD, Graham DI, Welsh FA, Budd WW (1979) Diffuse cerebral ischemia in the cat: III. Neuropathological sequelae of severe ischemia. Ann Neurol5:350–358

    Google Scholar 

  26. Hallenbeck JM, Furlow TW (1978) Influence of several plasma fractions on post-ischemic microvascular reperfusion in the central nervous system. Stroke 9:375–382

    Google Scholar 

  27. Hallenbeck JM, Furlow TW, Ruel TA, Greenbaum LJ (1979) Extracorporeal glass-wool filtration of whole blood enhances post-ischemic recovery of the cortical sensory evoked response. Stroke 10:158–164

    Google Scholar 

  28. Horton RW, Meldrum BS, Pedley TA, McWilliam JR (1980) Regional cerebral blood flow in the rat during prolonged seizure activity. Brain Res 192:399–412

    Google Scholar 

  29. Hossmann K-A, Sato K (1970) The effect of ischemia on sensorimotor cortex of cat: Electrophysiological, biochemical, and electron-microscopical observations. Z Neurol 198:33–45

    Google Scholar 

  30. Hossmann K-A, Lechtape Gruter H, Hossmann V (1973) The role of the cerebral blood flow for the recovery of the brain after prolonged ischemia. Z Neurol 204:281–299

    Google Scholar 

  31. Hossmann K-A, Kleihues P (1973) Reversibility of ischemic brain damage. Arch Neurol 29:375–384

    Google Scholar 

  32. Hossmann K-A, Hossmann V (1977) Coagulopathy following experimental cerebral ischemia. Stroke 8:249–254

    Google Scholar 

  33. Hossmann K-A, Hossmann V, Takagi S (1978) Microsphere analysis of local cerebral and extracerebral blood flow after complete ischemia of the cat brain for one hour. J Neurol 248:275–285

    Google Scholar 

  34. Jenkins LW,Povlishock JT, Becker DP, Miller JD, Sullivan HG (1979) Complete cerebral ischemia: An ultrastructural study. Acta Neuropathol (Berl) 48:113–125

    Google Scholar 

  35. Kalimo H, Garia JH, Kamijyo Y, Tanaka J, Trump BF (1977) The ultrastructure of “brain death”. II. Electron microscopy of feline cortex after complete ischemia. Virchows Arch B [Cell Pathol] 25:207–220

    Google Scholar 

  36. Kalimo H, Paljarvi L, Vapalahti M (1979) The early ultrastructural alterations in the rabbit cerebral and cerebellar cortex after compression ischaemia. Neuropathol Appl Neurobiol 5:211–223

    Google Scholar 

  37. Kalimo H, Agardh C-D, Olsson Y, Siesjo BK (1980) Hypoglycemic brain injury. II. Electron microscopic findings in rat cerebral cortical neurons during profound insulin-induced hypoglycemia and in the recovery period following glucose administration. Acta Neuropathol (Berl) 50:43–52

    Google Scholar 

  38. Kinter D, Costello DJ, Levin AB, Gilboe DD (1980) Brain metabolism after 30 minutes of hypoxic or anoxic perfusion or ischemia. Am J Physiol 239:E501-E509

    Google Scholar 

  39. Klatzo I (1975) Pathophysiologic aspects of cerebral ischemia. In: Tower DB (ed) The basic neurosciences. The nervous system, vol 1, pp 313–322

  40. Kofke WA, Nemoto EM, Hossmann K-A, Taylor F, Kessler PD, Stezoski SW (1979) Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys. Stroke 10:554–560

    Google Scholar 

  41. Kogure K, Morooka H, Busto R, SCheinberg P (1979) Involvement of lipid peroxidation in postischemic brain damage. Neurology 29:546

    Google Scholar 

  42. Kogure K, Busto R, Schwartzman RJ, Scheinberg P (1980) The dissociation of cerebral blood flow, metabolism, and function in the early stages of developing cerebral infarction. Ann Neurol 8:278–290

    Google Scholar 

  43. Kontos HA, Wei EP, Povlishock JT, Dietrich WD, Ellis EF, Magiera CG (1980) Cerebral arteriolar damage by arachidonic acid and prostaglandin G2. Science 209:1242–1245

    Google Scholar 

  44. Leniger-Follert E, Hossmann K-A (1977) Microflow and cortical oxygen pressure during and after prolonged cerebral ischemia. Brain Res 124:158–161

    Google Scholar 

  45. Levy DE, Brierley JB, Plum F (1975) Ischaemic brain damage in the gerbil in the absence of “no-reflow”. J Neurol Neurosurg Psychiat 38:1197–1205

    Google Scholar 

  46. Levy DE, Brierley JB (1979) Delayed pentobarbital administration limits ischemic brain damage in gerbils. Ann Neurol 5:59–64

    Google Scholar 

  47. Levy DE, Van Uitert RL, Pike CL (1979) Delayed postischemic hypoperfusion: A potentially damaging consequence of stroke. Neurology 29:1245–1252

    Google Scholar 

  48. Majewska MD, Strosznajder J, Lazarewicz J (1978) Effect of ischemic anoxia and barbiturate anesthesia on free radical oxidation of mitochondrial phospholipids. Brain Res 158:423–434

    Google Scholar 

  49. Marshall LF, Graham DI, Durity F, Lounsbury R, Welsh F, Langfitt TW (1975) Experimental cerebral oligemia and ischemia produced by intracranial hypertension. Part 2: Brain morphology. J Neurosurg 43:318–322

    Google Scholar 

  50. Michenfelder JD, Milde JH, Sundt TM (1976) Cerebral protection by barbiturate anesthesia. Arch Neurol 33:345–350

    Google Scholar 

  51. Miller CL, Lampard DG, Alexander K, Brown WA (1980) Local cerebral blood flow following transient cerebral ischemia. I. Onset of impaired reperfusion within the first hour following global ischemia. Stroke 11:534–541

    Google Scholar 

  52. Nemoto EM, Snyder JV, Carroll RG, Morita H (1975) Global ischemia in dogs: Cerebrovascular CO2 reactivity and autoregulation. Stroke 6:425–431

    Google Scholar 

  53. Nemoto EM, Erdmann W, Strong E, Rao GR, Moossy J (1979) Regional brain pO2 after global ischemia in monkeys: Evidence for regional differences in critical perfusion pressures. Stroke 10:44–52

    Google Scholar 

  54. Nordstrom CH, Rehncrona S, Siesjo BK (1977) Restitution of cerebral energy state as well as of glycolytic metabolites, citric acid cycle intermediates and associated amino acids after 30 minutes of complete ischemia in rats anesthetized with nitrous oxide or phenobarbital. J Neurochem 30:479–486

    Google Scholar 

  55. Olsson Y, Hossmann K-A (1971) The effect of intravascular saline perfusion on the sequelae of transient cerebral ischemia: Light and electron-microscopical observations. Acta Neuropathol (Berl) 17:68–79

    Google Scholar 

  56. Rehncrona S, Mela L, Siesjo BK (1979) Recovery of brain mitochondrial function in the rat after complete and incomplete cerebral ischemia. Stroke 10:437–446

    Google Scholar 

  57. Safar P, Stezoski W, Nemoto EM (1976) Amelioration of brain damage after 12 minutes cardiac arrest in dogs. Arch Neurol 33:91–95

    Google Scholar 

  58. Siesjo BK (1978) Ischemia. In: Brain energy metabolism. Wiley, Chichester New York Brisbane Toronto, pp 453–526

    Google Scholar 

  59. Siesjo BK, Abdul-Rahman A (1979) Delayed hypoperfusion in the cerebral cortex of the rat in the recovery period following severe hypoglycemia. Acta Physiol Scand 106:375–376

    Google Scholar 

  60. Siesjo BK, Abdul-Rahman A (1979) A metabolic basis for the selective vulnerability of neurons in status epilepticus. Acta Physiol Scand 106:377–378

    Google Scholar 

  61. Spagnuolo C, Sautebin L, Galli G, Ralagni G, Galli C, Mazzari S, Finesso M (1980) PGF2α, thromboxane B2 and HETE levels in gerbil brain cortex after ligation of common carotid arteries and decapitation. Prostaglandins 18:53–61

    Google Scholar 

  62. Steen PA, Milde JH, Michenfelder JD (1979) No barbiturate protection in a dog model of complete cerebral ischemia. Ann Neurol 5:343–349

    Google Scholar 

  63. Takagi S, Cocito L, Hossmann K-A (1977) Blood recirculation and pharmacological responsiveness of the cerebral vasculature following prolonged ischemia of cat brain. Stroke 8:707–712

    Google Scholar 

  64. Trump BF, Croker BP, Mergner WJ (1971) The role of energy metabolism, ion and water shifts in the pathogenesis of cell injury. In: Richter GW (ed) Cell membranes, biological and pathological aspects. Williams and Wilkins, Baltimore, pp 88–128

    Google Scholar 

  65. Trump BF, Berezesky IK, Collan Y, Kahng MW, Mergner WJ (1976) Recent studies on the pathophysiology of ischemic cell injury. Beitr Pathol 158:363–388

    Google Scholar 

  66. Waggener JD, Beggs JL (1977) Parenchymal effects of hypoxic ischemia. In: Thompson RA, Green JR (eds) Stroke. Adv Neurol 16:21–30

  67. Yoshida S, Inoh S, Asano T, Sano K, Kubota M, Shimazaki H, Ueta N (1980) Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. J Neurosurg 53:323–331

    Google Scholar 

Download references

Author information

Author notes

  1. W. Lewelt

    Present address: Dept. of Anesthesiology, Medical Academy of Lublin, Poland

  2. J. D. Miller

    Present address: Dept. of Surgical Neurology, University of Edinburg, Scotland

Authors and Affiliations

  1. Dept of Neurological Surgery, MCV Station, Medical College of Virginia, Virginia Commonwealth University, Box 709, 23298, Richmond, VA, USA

    L. W. Jenkins, W. Lewelt, J. D. Miller & D. P. Becker

  2. Dept of Anatomy, MCV Station, Medical College of Virginia, Virginia Commonwealth University, Box 709, 23298, Richmond, VA, USA

    L. W. Jenkins & J. T. Povlishock

Authors
  1. L. W. Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. T. Povlishock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Lewelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. D. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. P. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by PHS Grant NS-12587

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jenkins, L.W., Povlishock, J.T., Lewelt, W. et al. The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia. Acta Neuropathol 55, 205–220 (1981). https://doi.org/10.1007/BF00691320

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00691320

Key words

Search

Navigation