Skip to main content
Log in

Ultrastructural and ionic studies in global ischemic dog brain

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

A time course of tissue ionic changes, and their relation to ultrastructural findings during reperfusion following a 15-min global ischemic brain insult was studied in a dog model. Parietal cortex was analyzed for Ca, Na, K, Mg and Fe in controls and after 10 min, 2, 4, and 8 h of reperfusion. After 8 h of reperfusion, the mean values (μmol/g tissue wet wt.) for Ca (control=1.43, 8 h=2.76) and Na (control 60.4, 8 h=107.4) doubled and K (control=90.4, 8 h=48.5) decreased to half that of the control. Ultrastructural studies and subcellular localization of calcium in parietal cortex of in situ-fixed brains after 8 h showed cortical neurons with clumping of nuclear chromatin, dilatation of endoplasmic reticulum and disruption of plasma membranes. Large amounts of electron-dense precipitates of calcium were present within dilated astrocytic processes, synaptic vesicles, cytoplasm of edematous dendrites and mitochondria. Cortical neurons from postischemic dogs without reperfusion showed only slight chromatin clumping and edema of astrocytic processes, but no calcium accumulation. The large ionic shifts noted between 4 and 8 h of reperfusion, indicate a progressive inability of the cells to maintain normal transmembrane gradients of these ions and may reflect a membrane destructive process, as demonstrated ultrastructurally at 8 h. Enhanced calcium entry into the neuron during reperfusion appears to be a part of the cytotoxic mechanism leading to neuronal necrosis.

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

Access this article

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, Kowade 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 KA, 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. Borgers M, DeBrander M, Van Reempts J, Avouters F, Jacob WA (1977) Intranuclear microtubules in lung mast cells of guinea pigs in anaphylactic shock. Lab Invest 37:1–8

    Google Scholar 

  4. Borgers M, Thone F, Van Neuten JM (1981) The subcellular distribution of calcium and the effects of calcium antagonists as evaluated with a combined oxalate-pyroantimonate technique. Acta Histochem [Suppl] 24:327–332

    Google Scholar 

  5. Brierly JB, Graham DI (1984) Hypoxia and vascular disorders of the central nervous system. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's neuropathology vol 4. Wiley Medical, New York, pp 125–156

    Google Scholar 

  6. Dearden NM (1985) Ischemic brain. Lancet ii:255–259

    Google Scholar 

  7. Demopoulous MB, Flamm ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major CNS disorders. Acta Physiol Scand [Suppl] 492:91–119

    Google Scholar 

  8. Diculescu I, Popescu LM, Jonescu N (1971) Electron microscope demonstration of calcium in the heart mitochondria in situ. Exp Cell Res 68:210–214

    Google Scholar 

  9. Farber JL, Kenneth MD, Chien R, Mittnacht S (1981) The pathogenesis of irreversible cell injury in ischemia. Am J Pathol 102:271–281

    Google Scholar 

  10. Garcia JM (1984) Experimental ischemic stroke: a review. Stroke 15:5–14

    Google Scholar 

  11. Harris RJ, Symon L, Branston NM, Bahyhan M (1981) Changes in intracellular calcium activity in cerebral ischemia. J Cereb Blood Flow Metab 1:203–209

    Google Scholar 

  12. Hossmann KA, Sato K (1970) The effect of ischemia on sensorimotor cortex of cat: electrophysiologic biochemical, and electron microscopic observations. J Neurol 198:33–45

    Google Scholar 

  13. Hossmann KA, Sasaki S, Zimmermann V (1977) Cation activities in reversible ischemia of the cat brain. Stroke 8:77–81

    Google Scholar 

  14. Hossmann KA, Paschen W, Csiba L (1983) Relationship between calcium accumulation and recovery of cat brain after prolonged cerebral ischemia. J Cereb Blood Flow Metab 3:346–351

    Google Scholar 

  15. Jalenko C, Wheeler M, Callaway D (1978) Shock and resuscitation. II: Volume repletion with minimal edema using HALFD method. J Amm Coll Emerg Phys 7:326–331

    Google Scholar 

  16. Jenkins LW, Povlishock JT, Becker DP, Miller JD, Sullivan HG (1979) Complete cerebral ischemia: an ultrastructural study. Acta Neuropathol (Berl) 45:113–125

    Google Scholar 

  17. Jenkins LW, Povishock JT, Lewelt W, Miller JD, Becker DP (1981) The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia. Acta Neuropathol (Berl) 55:205–220

    Google Scholar 

  18. Kalimo H, Garcia 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] 25:207–220

    Google Scholar 

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

    Google Scholar 

  20. Kalimo H, Rehncorona S, Soderfeldt B, Olsson Y, Siesjo BK (1981) Brain lactic acidosis and ischemic cell damage. 2. Histopathology. J Cereb Blood Flow Metab 1:313–327

    Google Scholar 

  21. Karlsson U, Schultz RL (1966) Fixation of the central nervous system by aldehyde perfusion. III. Structural changes after exsanguination and delayed perfusion. J Ultrastr Res 14:47–56

    Google Scholar 

  22. Klatzo I (1979) Cerebral ischemia. In: Smith WT, Cavanagh JB (eds) Recent advances in Neuropathology, vol 1. Churchill Livingstone, Edinbrugh, pp 27–40

    Google Scholar 

  23. Komara JS, Nayini NR, Bialick HA, Indrieri RJ Evans AT, Garritano AM, White BC, Aust SD (1986) Brain iron delocalization and lipid peroxidation following cardiac arrest. Ann Emerg Med 15:384–389

    Google Scholar 

  24. Matakas F, Cervos-Navarro J, Schneider H (1973) Experimental brain death. I. Morphology and fine structure of the brain. J Neurol Neurosurg Psychiatry 36:497–508

    Google Scholar 

  25. Mead JF (1976) Free radical mechanism in lipid damage and consequences for cellular membranes. In: Pryor WA (ed) Free radicals in biology, vol 1. Academic Press, New York, pp 51–62

    Google Scholar 

  26. Nemoto EM, Shiu GK, Nemmer JP, Bleyaert AL (1983) Free fatty acid accumulation in the pathogenesis and therapy of cerebral ischemic anoxic injury. Am J Emerg Med 1:175–179

    Google Scholar 

  27. Nemoto EM, Bleyaert AL, Stezoski SW, Moossy J, Rao YR, Safar P (1977) Global brain ischemia: a reproducible monkey model. Stroke 8:558–564

    Google Scholar 

  28. Rehncrona S, Abdul Rahman A, Siesjo BK (1979) Local cerebral blood flow in the post ischemic period. Acta Neurol Scand [Suppl] 60:294–295

    Google Scholar 

  29. 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 

  30. Rosenthal RE, Hamud F, Fiskum G (1986) Cerebral ischemia and reperfusion: mitochondrial injury and recovery. Ann Emerg Med 15:631

    Google Scholar 

  31. Siemkowicz E, Hansen AJ (1981) Brain extracellular ion composition and EEG activity following 10 min ischemia in normo- and hyperglycemic rats. Stroke 12:236–240

    Google Scholar 

  32. Siesjo BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:155–185

    Google Scholar 

  33. Simon RP, Griffiths T, Evans MC, Swan JH, Meldrum BS (1984) Calcium over-load in selectively vulnerable neurons of the hippocampus during and after ischemia: an electron microscopy study in the rat. J Cereb Blood Flow Metab 4:350–361

    Google Scholar 

  34. Trump BF, Arstila AU (1975) Cellular reaction to injury. In: La Via MF, Hill RB (eds) Principles of pathobiology, 2nd edn. Oxford University Press, New York, pp 9–96

    Google Scholar 

  35. Van Reempts J, Borgers M (1985) Ischemic brain injury and cell calcium: morphologic and therapeutic aspects. Ann Emerg Med 14:736–741

    Google Scholar 

  36. Van Reempts J, Borgers M, DeNollin SR, Garrevoet TC, Jacob WA (1984) Identification of calcium in the retina by the combined use of ultrastructural cytochemistry and laser microprobe mass analysis. J Histochem Cytochem 32:788–792

    Google Scholar 

  37. Watson BD, Busto R, Goldberg WJ, Goldbert SM, Shinichi Y, Ginzberg MD (1984) Lipid peroxidation in vivo induced by reversible global ischemia in rat brain. J Neurochem 42:268–274

    Google Scholar 

  38. White BC, Winegar CD, Jackson RE, Joyce KM, Vigor DN, Hoehner TJ, Wilson RF (1983) Cerebral cortical perfusion during and following resuscitation from cardiac arrest in dogs. Am J Emerg Med 1:128–138

    Google Scholar 

  39. Winegar CD, White BC (1983) Physiology of resuscitation. Emerg Med Clinics NA 1:479–499

    Google Scholar 

  40. Yanagihara T, McCall JT (1982) Ionic shift in cerebral ischemia. Life Sci 30:1921–1925

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Contract No DAMD 85-17-4200 from the United States Army Medical Research and Development Command and a grant from the College of Human Medicine, Michigan State University. This work was presented at the 70th Annual Meeting of the American Association of Pathology, St. Louis, MO, April 16, 1986

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, K., Goosmann, M., Krause, G.S. et al. Ultrastructural and ionic studies in global ischemic dog brain. Acta Neuropathol 73, 393–399 (1987). https://doi.org/10.1007/BF00688266

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688266

Key words

Navigation