| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Effects of deprivation of oxygen and/or glucose on CA1 neurones in rat hippocampal sliced (kept at 36.5 ﾟC) were studied by intracellular recording methods.
The lack of oxygen or glucose caused a transient hyperpolarization followed by a slow depolarization at a plateau level of about 25 mV from the control resting potential. When oxygen or glucose was readmitted during the period of slow depolarization, the membrane potential and input resistance returned to the control levels. The results suggest that a low oxygen tension or a low glucose concentration pre se may not be the major cause of neuronal dysfunction due to brain ischaemia.
The oxygen and glucose lack caused a transient hyperpolarization, a subsequent slow depolarization, and then a rapid depolarization after 5-7 min of deprivation. When oxygen and glucose were readmitted during the period of rapid depolarization, the membrane potential did not repolarize, but became 0 mV; the neurone showed no functional recovery. Intracellul
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ar free Ca concentration (estimated using the slices loaded with fura-2) gradually increased during the initial hyperpolarization and markedly elevated during the rapid depolarization. The threshold for generating the rapid depolarization varied between individual cells (-60 to -20 mV).
The rapid depolarization was not significantly affected by addition of or a non-NMDA-antagonist CNQX, or reduction in extracellular Na, K or Cl. On the other hand, removal of Ca, addition of Co, flunarizine, an NMDA antagonist APV or procaine, and intracellular injection of ATP prolonged the latency for generating the rapid depolarization. From these results, a minimal hypothesis for the progression of cell dysfunction during the deprivation of oxygen and glucose can be constructed: (1) decrease in intracellular ATP, (2) increase in cytosolic Ca concentration, (3) disturbance of membrane-cytoskeleton connections, (4) focal weakening of the cell surface, (5) expansion of weakened area (large blebs) leading to membrane hyperpermeability, and (6) collapse of ionic gradients and membrane dysfunction. Less
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