Excitatory Amino Acid and Purinergic Transmitter Involvement in Ischemia-Induced Selective Neuronal Death
We have examined the effects of noncompetitive N-methyl-D-aspartate receptor antagonists (MK-801; LY154045), kainate/quisqualate receptor antagonists (glutamyltaurine; γ-aminomethylsulphonic acid), and adenosine A1 receptor agonists on selective nerve cell death in an unanesthetized rat model of transient forebrain ischemia. The N-methyl-D-aspartate, kainate, and quisqualate receptor antagonists, either singly or in combination, failed to attenuate striatal or hippocampal damage. In contrast, the adenosine A1 receptor agonist, R-phenylisopropyladenosine, and the A1 and A2 receptor agonist, N-ethylcarboxamidoadenosine, significantly (p< 0.01) reduced CA1 pyramidal cell death in hippocampus. Excitatory amino acid neurotransmitter-mediated excitation appears not to play a major role in the pathogenesis of selective neuronal damage in this rat model. The ability of adenosine receptor agonists to attenuate hippocampal neuronal damage must be mediated via mechanisms other than inhibition of excitatory amino acid release. These results indicate that abnormalities of adenosinergic transmission are an important factor in ischemic injury to CA1 hippocampal pyramidal neurons.
KeywordsExcitatory Amino Acid Ischemic Damage Transient Forebrain Ischemia Adenosine Receptor Agonist Vulnerable Neuron
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