Although cytokine production by activated glia precedes the apoptotic loss of hippocampal neurons in brains from scrapie-infected mice (47), the experiments presented here suggest that TNF-α and IL-6 alone do not play a critical role in the development of pathology in the CNS. Therefore, the apparent resistance of TNF-α−/− mice to i.p. challenge with scrapie could not be attributed to a role of TNF-α in the development of pathology in the CNS. Our experiments strongly suggest that the effects of TNF-α operate at a peripheral stage, prior to neuroinvasion.
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