Calcium 45 Accumulation in the Dentate Hilus: Possible Effect of NMDA Receptor Blockers

  • H. Benveniste
  • P. C. Hüttemeier
  • F. F. Johansen
  • N. H. Diemer


Among the many complex reactions involved in ischemia-induced neuronal cell injury, intracellular calcium accumulation appears to be particularly cytotoxic [11, 19, 24]. The rise in the intracellular calcium concentration has been postulated to initiate or represent a “final common pathway” for cell death [23]. The mechanisms of intracellular calcium accumulation during neuronal injury are the result of several factors, but one source might be the opening of postsynaptic NMDA receptor-coupled calcium channels by excessive transmitter release of glutamate and aspartate [2].


NMDA Receptor 45Ca Content Cereb Blood Flow Microdialysis Probe Final Common Pathway 
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.
    Anis NA, Berry NR, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79:565–575PubMedGoogle Scholar
  2. 2.
    Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374PubMedCrossRefGoogle Scholar
  3. 3.
    Benveniste H (1989) Brain microdialysis, short review. J Neurochem 52Google Scholar
  4. 4.
    Benveniste H, Diemer NH (1988) Early postischemic 45Ca accumulation in rat dentate hilus. J Cereb Blood Flow Metab 8:713–719PubMedCrossRefGoogle Scholar
  5. 5.
    Block GA, Pulsinelli WA (1987) N-Methyl-D-aspartate receptor antagonists: failure to prevent ischemia-induced selective neuronal damage. In: Powers WJ, Raichle ME (eds) Cerebrovascular diseases, 15th Research (Princeton) Conference, pp 37–45Google Scholar
  6. 6.
    Brierley JB (1976) Cerebral hypoxia. In: Blackwood W, Corsellis JAN (eds) Greenfields neuropathology, pp 43–85Google Scholar
  7. 7.
    Cavero I, Spedding M (1983) “Calcium antagonists”: a class of drugs with a bright future. Part I. Cellular calcium homeostasis and calcium as a coupling messenger. Life Sci 33:2571–2581PubMedCrossRefGoogle Scholar
  8. 8.
    Chien KR, Abrams J, Richard G, Farber JL (1977) Prevention by chlorpromazine of ischemic liver cell death. Am J Pathol 88:539–557PubMedGoogle Scholar
  9. 9.
    Diemer NH, Siemkowicz E (1981) Regional neurone damage after cerebral ischemia in the normo-and hypoglycemic rat. Neuropathol Appl Neurobiol 7:217–227PubMedCrossRefGoogle Scholar
  10. 10.
    Dienel GA (1984) Regional accumulation of calcium in postischemic rat brain. J Neurochem 43:913–925PubMedCrossRefGoogle Scholar
  11. 11.
    Hass WK (1981) Beyond cerebral blood flow, metabolism and ischemic thresholds: examination of the role of calcium in the initiation of cerebral infarction. In: Meyer JS, Lechner H, Reivich M, Ott EO, Arabinar A (eds) Cerebral vascular disease, vol 3. Proceedings of the 10th Salzburg Conference on cerebral vascular disease. Excerpta Medica, Amsterdam, pp 3–17Google Scholar
  12. 12.
    Herrling PL, Morris R, Salt TE (1983) Effects of excitatory amino acids and their antagonists on membrane and action potentials of rat caudate neurones. J Physiol 339:207–222PubMedGoogle Scholar
  13. 13.
    Hossman KA, Paschen W, Csiba L (1983) Relationship between calcium accumulation and recovery of cat brain after prolonged ischemia. J Cereb Blood Flow Metab 3:346–353CrossRefGoogle Scholar
  14. 14.
    Ito U, Spatz JT, Walker Jr, Klatzo I (1975) Experimental cerebral ischemia in mongolian gerbils. I. Light microscopic observations. Acta Neuropathol 68:230–238Google Scholar
  15. 15.
    Johansen FF, Zimmer J, Diemer NH (1987) Early loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat precedes CA-1 pyramidal loss. Acta Neuropathol (Berl) 73:110–114CrossRefGoogle Scholar
  16. 16.
    Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69PubMedCrossRefGoogle Scholar
  17. 17.
    MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker LJ (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321:519–522PubMedCrossRefGoogle Scholar
  18. 18.
    Mayer ML, Gary L, Westbrook GL, Guthrie PG (1984) Voltage-dependent block by Mg++ of NMDA responses in spinal cord neurones. Nature 309:261–263PubMedCrossRefGoogle Scholar
  19. 19.
    Meldrum BS (1983) Metabolic factors during prolonged seizures and their relation to nerve cell death. Adv Neurol 34:261–275PubMedGoogle Scholar
  20. 20.
    Nowak L, Bregestovski P, Ascher P, Herbert A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307:462–465PubMedCrossRefGoogle Scholar
  21. 21.
    Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498PubMedCrossRefGoogle Scholar
  22. 22.
    Schwartzkroin PA, Wyler AR (1980) Mechanisms underlying epileptiform burst discharge. Ann Neurol 7:95–107PubMedCrossRefGoogle Scholar
  23. 23.
    Shanne FAX, Kane AB, Young EE, Farber JL (1979) Calcium dependence of toxic cell death: a final common pathway. Science 206:700–702CrossRefGoogle Scholar
  24. 24.
    Siesjö BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metabol 1:155–185CrossRefGoogle Scholar
  25. 25.
    Suzuki R, Yamaguchi T, Li CL, Klatzo I (1983) The effects of 5-min ischemia in mongolian gerbils. II. Changes of spontaneous neuronal activity in cerebral cortex and CA-1 sector of hippocampus. Acta Neuropathol 60:217–222PubMedCrossRefGoogle Scholar
  26. 26.
    Wrong RKS, Prince DA (1978) Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 159:385–390CrossRefGoogle Scholar
  27. 27.
    Wrong RKS, Prince DA, Basbaum AI (1979) Intradendritic recordings from hippocampal neurons. Proc Natl Acad Sci USA 76:986–990CrossRefGoogle Scholar
  28. 28.
    Zimmer J, Sunde N (1984) Neuropeptides and astroglia in intracerebral hippocampal transplants: an immunohistochemical study in the rat. J Comp Neurol 227:331–347PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • H. Benveniste
    • 1
  • P. C. Hüttemeier
    • 2
  • F. F. Johansen
    • 1
  • N. H. Diemer
    • 1
  1. 1.PharmaBioTec Research Center, Institute of NeuropathologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Anesthesiology, Glostrup HospitalUniversity of CopenhagenCopenhagenDenmark

Personalised recommendations