Effect of Calcium Antagonists on Cerebral Blood Flow, Protein Synthesis, and Histopathology After Global Ischemia of Gerbil Brain

  • M. Kocher
  • Y. Xie
  • G. Brinker
  • E. Dux
  • K.-A. Hossmann
Conference paper


Under physiological conditions the intracellular concentration of free calcium (10−7 mol/l) is about four orders of magnitude lower than the concentration in the extracellular space (10−3 mol/l) [16]. If local cerebral flow is reduced to about 10 ml/100 g/min, neurons depolarize and extracellular calcium enters the cell across voltage-dependent channels [12]. The resulting calcium overload of the cytosol has been discussed as triggering a series of pathophysiological processes leading to the manifestation of ischemic neuronal injury [26].


Cerebral Blood Flow Calcium Antagonist Global Ischemia Cereb Blood Flow Cortical Blood Flow 
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  1. 1.
    Alps BJ, Hass WK (1987) The potential beneficial effect of nicardipine in a rat model of transient forebrain ischemia. Neurology 37:809–814PubMedCrossRefGoogle Scholar
  2. 2.
    Arai H, Passonneau JV, Lust WD (1986) Energy metabolism in delayed neuronal death of CA1 neurons of the hippocampus following transient ischemia in the gerbil. Metab Brain Dis 1:263–278PubMedCrossRefGoogle Scholar
  3. 3.
    Cooper HK, Zalewska T, Kawakami S, Hossmann K-A, Kleihues P (1977) The effect of ischaemia and recirculation on protein synthesis in the rat brain. J Neurochem 28:929–934PubMedCrossRefGoogle Scholar
  4. 4.
    Deshpande JK, Wieloch T (1986) Flunarizine, a calcium entry blocker, ameliorates ischemia brain damage in the rat. Anesthesiology 64:215–224PubMedCrossRefGoogle Scholar
  5. 5.
    Deshpande JK, Siesjö BK, Wieloch T (1987) Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. J Cereb Blood Flow Metab 7:89–95PubMedCrossRefGoogle Scholar
  6. 6.
    Dienel GA (1984) Regional accumulation of calcium in postischemic rat brain. J Neurochem 43:913–925PubMedCrossRefGoogle Scholar
  7. 7.
    Dienel GA, Pulsinelli WA, Duffy TE (1980) Regional protein synthesis in rat brain following acute hemispheric ischemia. J Neurochem 35:1216–1226PubMedCrossRefGoogle Scholar
  8. 8.
    Dux E, Mies G, Hossmann K-A, Siklos L (1987) Calcium in the mitochondria following brief ischemia of gerbil brain. Neurosci Lett 89:295–300CrossRefGoogle Scholar
  9. 9.
    Greenberg DA (1987) Calcium channels and calcium channel antagonists. Ann Neurol 21:317–330PubMedCrossRefGoogle Scholar
  10. 10.
    Grotta J, Spydell J, Pettigrew C, Ostrow P, Hunter D (1986) The effect of nicardipine on neuronal function following ischemia. Stroke 17:213–219PubMedCrossRefGoogle Scholar
  11. 11.
    Harper AM, Craigen L, Kazda S (1981) Effect of the calcium antagonist, nimodipine, on cerebral blood flow and metabolism in the primate. J Cereb Blood Flow Metab 1:349–356PubMedCrossRefGoogle Scholar
  12. 12.
    Harris RJ, Symon L (1984) Extracellular pH, potassium, and calcium activities in progressive ischaemia of rat cortex. J Cereb Blood Flow Metab 4:178–186PubMedCrossRefGoogle Scholar
  13. 13.
    Hossmann K-A, Grosse Ophoff B, Schmidt-Kastner R, Oschlies U (1985) Mitochondrial calcium sequestration in cortical and hippocampal neurons after prolonged ischemia of the cat brain. Acta Neuropathol 68:230–238PubMedCrossRefGoogle Scholar
  14. 14.
    Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69PubMedCrossRefGoogle Scholar
  15. 15.
    Kirino T, Sano K (1984) Fine structural nature of delayed neuronal death following ischemia in the gerbil hippocampus. Acta Neuropathol 62:209–218PubMedCrossRefGoogle Scholar
  16. 16.
    McBurney RN, Neering IR (1987) Neuronal calcium homeostasis. TINS 10:164–169Google Scholar
  17. 17.
    Mies G, Paschen W, Hossmann K-A, Klatzo I (1983) Simultaneous measurement of regional blood flow and metabolism during maturation of hippocampal lesions following short-lasting cerebral ischemia in gerbils. J Cereb Blood Flow Metab 3(Suppl 1):329–330Google Scholar
  18. 18.
    Milde LN, Milde JH, Michenfelder JD (1986) Delayed treatment with nimodipine improves cerebral blood flow after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 6:332–337PubMedCrossRefGoogle Scholar
  19. 19.
    Mohamed AA, McCulloch J, Mendelow AD, Teasdale GM, Harper AM (1984) Effect of the calcium antagonist nimodipine on local cerebral blood flow: relationship to arterial blood pressure. J Cereb Blood Flow Metab 4:206–211PubMedCrossRefGoogle Scholar
  20. 20.
    Munekata K, Hossmann K-A (1987) Effect of 5-minute ischemia on regional pH and energy state of the gerbil brain: relation to selective vulnerability of the hippocampus. Stroke 18:412–417PubMedCrossRefGoogle Scholar
  21. 21.
    Nicholls DG, Akerman KEO (1982) Mitochondrial calcium transport. Biochim Biophys Acta 683:57–88PubMedGoogle Scholar
  22. 22.
    Nowak TS Jr, Fried RL, Lust WD, Passonneau JV (1985) Changes in brain energy metabolism and protein synthesis following transient bilateral ischemia in the gerbil. J Neurochem 44:487–494PubMedCrossRefGoogle Scholar
  23. 23.
    Sakabe T, Nagai I, Ishikawa T, Takeshita H, Masuda T, Matsumoto M, Tateishi A (1986) Nicardipine increases cerebral blood flow but does not improve neurologic recovery in a canine model of complete cerebral ischemia. J Cereb Blood Flow Metab 6:684–690PubMedCrossRefGoogle Scholar
  24. 24.
    Sakamoto N, Kogure K, Kato H, Ohtomo H (1986) Disturbed Ca+ homeostasis in the gerbil hippocampus following brief transient ischemia. Brain Res 364:372–376PubMedCrossRefGoogle Scholar
  25. 25.
    Siemkowicz E, Hansen AJ (1981) Brain extracellular ion composition and EEG activity following 10 minutes ischemia in normo-and hyperglycemic rats. Stroke 12:236–240PubMedCrossRefGoogle Scholar
  26. 26.
    Siesjö BK, Wieloch T (1985) Cerebral metabolism in ischaemia: neurochemical basis for therapy. Br J Anaesth 57:47–62PubMedCrossRefGoogle Scholar
  27. 27.
    Smith M-L, Kagström E, Rosén I, Siesjö BK (1983) Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat. J Cereb Blood Flow Metab 3:543–546PubMedCrossRefGoogle Scholar
  28. 28.
    Simon RP, Griffiths T, Evans MC, Swan JH, Meldrum BS (1984) Calcium overload in selectively vulnerable neurons of the hippocampus during and after ischemia: an electron microscopy study in the rat. J Cereb Blood Flow Metab 4:350–361PubMedCrossRefGoogle Scholar
  29. 29.
    Steen PA, Newberg LA, Milde JH, Michenfelder JD (1983) Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 3:38–43PubMedCrossRefGoogle Scholar
  30. 30.
    Steen PA, Newberg LA, Milde JH, Michenfelder JD (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
  31. 31.
    Suzuki R, Yamaguchi T, Li C-L, Klatzo I (1983) The effects of 5-minute ischemia in Mongolian gerbils: II. Changes of spontaneous neuronal activity in cerebral cortex and CA1 sector of hippocampus. Acta Neuropathol 60:217–222PubMedCrossRefGoogle Scholar
  32. 32.
    Van Reempts J, Borgers M, Offner F (1982) Ultrastructural localization of calcium in the cat retina with combined oxalate-pyroantimonate technique. Histochem J 14:517–522PubMedCrossRefGoogle Scholar
  33. 33.
    Van Reempts J, Haseldonckx M, Deuren van B, Wouters L, Borgers M (1986) Structural damage of the ischemic brain: involvement of calcium and effects of postischemic treatment with calcium entry blockers. Drug Devel Res 8:387–395CrossRefGoogle Scholar
  34. 34.
    Vibulresth S, Dietrich WD, Busto R, Ginsberg MD (1987) Failure of nimodipine to prevent ischemic neuronal damage in rats. Stroke 18:210–216CrossRefGoogle Scholar
  35. 35.
    Xie Y, Hossmann K-A, Munekata K, Seo K (1987) Prolonged suppression of protein synthesis after brief cerebral ischemia in gerbils. In: Cervós-Navarro J, Ferszt R (eds) Stroke and microcirculation. Raven Press, New York, pp 135–14Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. Kocher
    • 1
  • Y. Xie
    • 1
  • G. Brinker
    • 1
  • E. Dux
    • 1
  • K.-A. Hossmann
    • 1
  1. 1.Department for Experimental NeurologyMax-Planck-Institute for Neurological ResearchKöln 91Germany

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