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.
Similar content being viewed by others
References
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
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
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
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
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
Dearden NM (1985) Ischemic brain. Lancet ii:255–259
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
Diculescu I, Popescu LM, Jonescu N (1971) Electron microscope demonstration of calcium in the heart mitochondria in situ. Exp Cell Res 68:210–214
Farber JL, Kenneth MD, Chien R, Mittnacht S (1981) The pathogenesis of irreversible cell injury in ischemia. Am J Pathol 102:271–281
Garcia JM (1984) Experimental ischemic stroke: a review. Stroke 15:5–14
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
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
Hossmann KA, Sasaki S, Zimmermann V (1977) Cation activities in reversible ischemia of the cat brain. Stroke 8:77–81
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
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
Jenkins LW, Povlishock JT, Becker DP, Miller JD, Sullivan HG (1979) Complete cerebral ischemia: an ultrastructural study. Acta Neuropathol (Berl) 45:113–125
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
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
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
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
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
Klatzo I (1979) Cerebral ischemia. In: Smith WT, Cavanagh JB (eds) Recent advances in Neuropathology, vol 1. Churchill Livingstone, Edinbrugh, pp 27–40
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
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
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
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
Nemoto EM, Bleyaert AL, Stezoski SW, Moossy J, Rao YR, Safar P (1977) Global brain ischemia: a reproducible monkey model. Stroke 8:558–564
Rehncrona S, Abdul Rahman A, Siesjo BK (1979) Local cerebral blood flow in the post ischemic period. Acta Neurol Scand [Suppl] 60:294–295
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
Rosenthal RE, Hamud F, Fiskum G (1986) Cerebral ischemia and reperfusion: mitochondrial injury and recovery. Ann Emerg Med 15:631
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
Siesjo BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1:155–185
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
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
Van Reempts J, Borgers M (1985) Ischemic brain injury and cell calcium: morphologic and therapeutic aspects. Ann Emerg Med 14:736–741
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
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
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
Winegar CD, White BC (1983) Physiology of resuscitation. Emerg Med Clinics NA 1:479–499
Yanagihara T, McCall JT (1982) Ionic shift in cerebral ischemia. Life Sci 30:1921–1925
Author information
Authors and Affiliations
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
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00688266