Postischemic changes in the binding of excitatory and inhibitory neurotransmitters in the gerbil brain

Abstract

We performed receptor autoradiography to determine sequential changes in the binding of N- methyl- D - aspartate (NMDA) and γ-aminobutyric acid A (GABA A) 1 h to 1 month after 10 min of transient cerebral ischemia in the gerbil. [ 3H]MK-801 and [ 3H]muscimol were used to label NMDA and GABA A receptors, respectively. [ 3H]MK-801 binding showed no significant changes in the striatum and hippocampus at an early stage (1–24 h) after ischemia. Thereafter, [ 3H]MK-801 binding exhibited a significant reduction in the dorsolateral striatum, most of hippocampal CA1 sector and dentate gyrus 48 h or 7 days of recirculation. However, [ 3H]MK-801 binding progressively depressed in the hippocampal CA1 sector 1 month after ischemia, whereas other regions showed no significant alteration in the binding. By contrast, [ 3H]muscimol binding was unchanged in all brain areas throughout the recirculation period. A histological study also demonstrated that transient ischemia caused severe neuronal damage in the striatum and hippocampus. These results demonstrate that NMDA and GABA A receptors are relatively resistant to severe degenerative processes. Furthermore, our finding suggests that transient ischemia may induce long-term changes in the properties of survival neurons or interneurons especially in the hippocampal CA1 sector.