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To address this issue directly, we created a mouse in which COX-2 is conditionally ablated in selected forebrain neurons. Results following pilocarpine-induced status epilepticus indicate that neuronal COX-2 promotes early neuroprotection and then delayed neurodegeneration of CA1 pyramidal neurons, promotes neurodegeneration of nearby somatostatin interneurons in the CA1 stratum oriens and dentate hilus (which themselves do not express COX-2), intensifies a broad inflammatory reaction involving numerous cytokines and other inflammatory mediators in the hippocampus, and is essential for development of a leaky blood\u2013brain barrier after seizures. 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