Neuron-Glia Interaction and Neural Network Function Involved in Ischemic Brain Damage.

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1. Slices of neocortex taken from P7-14 rats were labeled with fura-2. The [Ca^<2+>] _i was monitored pyramidal cells during O_2-glucose deprivation. Neurons in layer II/III showed significantly greater increases in [Ca^<2+>] _i than those in layers IV, V, or VI.The laminar difference in terms of the [Ca^<2+>] _i increases was primarily mediated by NMDA receptors. GABA might also act to increase [Ca^<2+>] _i during O_2-glucose deprivation. After a reduction in the Cl^- gradient, GABA induced a large [Ca^<2+>] _i increase mediated by NMDA receptor-channels. This indicates that a loss of the normal Cl^- gradient during ischemia might underlie the reduction and/or reversal of the GABAergic inhibition. Thus GABA may play an aggravating role in excitotoxicity if a shift in the Cl^- equilibrium potential occurs during cerebral ischemia.2. We have developed an optical imaging method of [Cl^-] _i in brain slices using 6-methoxy-N-ethylquinolinium iodide (MEQ). Slices of neocortex taken from P1 … More 0-14 rats were labeled with MEQ ; [Cl^-] ^i was monitored in individual neurons during O_2-glucose deprivation. A slight decrease followed by rather abmpt increase in [Cl^-] _i was induced by O_2-glucose deprivation. The former was mediated by an inhibition of Na^+, K^+-2Cl^- cotransporter. Such a shift in [Cl^-] _i induced by O_2-glucose deprivation would alter the GABAergic inhibition and may result in imbalance between inhibitory and excitatory systems.3.3-NPA-induced [Ca^<2+>] _i transients in mixed glial/neuronal cultures were investigated using fura-2.3-NPA irreversibly increased [Ca^<2+>] _i in astrocytes, but significantly to alesser extent in neurons. The [Ca^<2+>] _i increase in astrocytes was primarily promoted by a reverse operation of the Na^+-Ca^<2+> exchanger system, whereas in neurons, it was mediated by a different mechanism. In addition, 3-NPA killed 9% of astrocytes, while only 4% of neurons. This astrocytic cell death was preceded by blebbing of membranes and by abrupt [Ca^<2+>] _i surge following sustained [Ca^<2+>] _i increase. The results indicate that astrocytes are more vulnerable than neurons to 3-NPA-induced cellular Ca^<2+> overload and toxicity. Differential metabolism in energy production between astrocytes and neurons were suggested. Less