CONCLUSION:
We found that the combination of KA with an A1 adenosine receptor antagonist, CPT, induced significant neuronal cell loss in CA1 pyramidal neurons as well as in the CA3 subfield 4 days after i.c.v. injection. The activation of glial cells, such as morphological changes and the induction of MHC class II antigen, was limited to the CA3 subfield after the injection of KA alone. In contrast, treatment with KA/CPT also induced glial activation in the CA1 subfield. Although phosphorylated c-Jun, a critical marker of neuronal apoptosis, was not detected in vehicle-injected rat hippocampus, KA- and KA/CPT-injection induced phosphorylated c-Jun either in only the CA3 or in both the CA1 and the CA3, respectively. These results suggest that treatment with KA/CPT induced neurodegeneration in the CA1 through a mechanism similar to that of KA-induced neurodegeneration in the CA3. Coadministration of a specific agonist for A1 adenosine receptor, CHA, markedly attenuated the neuronal cell loss and glial activation. These results strongly suggest that endogenous adenosine has neuroprotective effects in pyramidal neurons of the hippocampus.

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