The Role of Spreading Depression-Like Hypoxic Depolarization in Irreversible Neuron Damage, and its Prevention

  • M. Balestrino
  • P. G. Aitken
  • L. S. Jones
  • G. G. Somjen
Part of the Advances in Behavioral Biology book series (ABBI, volume 35)


We investigated the role of spreading depression (SD)-like depolarization in hypoxic neuron damage. In hippocampal tissue slices, drugs that delayed the onset of the SD-like depolarization triggered by hypoxia (and therefore shortened the time spent in SD) also improved the chances of recovery of neural function after reoxygenation. The protective effect and the delay of SD onset were linked: in the few cases when SD was not delayed, neuronal function did not recover. By contrast, if SD-like depolarization was provoked (by high K+) early during hypoxia, functional recovery did not occur in spite of the presence of a protective drug. Dentate granule cells recovered function more frequently than did CA1 pyramidal cells, and during hypoxia SD-like depolarization began later and was milder in fascia dentata (FD) than in CA1 sector of hippocampal tissue slices. SD-induced damage was dependent on the availability of extracellular calcium: if Ca2+ was withdrawn before and during a hypoxic episode, then synaptic function recovered even after SD of extended duration. Iontophoretic injection of Ca2+ but not of Mg2+ into giant neurons of Aplysia caused irreversible loss of electric excitability and membrane impedance. We conclude that prolonged SD-like depolarization injures neurons because it allows excessive intracellular accumulation of calcium. We argue that SD is one, but not the only, mechanism by which hypoxic/ischemic neurons can be injured, and we advocate a multi-pronged approach to clinical management.


Brain Damage Spread Depression Population Spike Dentate Granule Cell Hypoxic Episode 
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.


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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • M. Balestrino
    • 1
  • P. G. Aitken
    • 1
  • L. S. Jones
    • 2
  • G. G. Somjen
    • 1
  1. 1.Departments of PhysiologyDuke UniversityDurhamUSA
  2. 2.Departments of PediatricsDuke UniversityDurhamUSA

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