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In contrast, adult DRG neurons survive permanent axotomy<jats:italic>in vivo<\/jats:italic>and in defined culture media devoid of exogenous neurotrophic factors<jats:italic>in vitro<\/jats:italic>. Peripheral axotomy in adult rats induces local accumulation of the cytokine tumor necrosis factor \u03b1 (TNF\u03b1), a potent activator of NF-\u03baB activity. We tested the hypothesis that activation of NF-\u03baB stimulated by endogenous TNF\u03b1 was required for survival of axotomized adult sensory neurons. Peripheral axotomy of lumbar DRG neurons by sciatic nerve crush induced a very rapid (within 2 h) and significant elevation in NF-\u03baB-binding activity. This phenomenon was mimicked in cultured neurons in which there was substantial NF-\u03baB nuclear translocation and a significant rise in NF-\u03baB DNA-binding activity after plating. Inhibitors of NF-\u03baB (SN50 or NF-\u03baB decoy DNA) resulted in necrotic cell death of medium to large neurons (\u226540 \u03bcm) within 24 h (60 and 75%, respectively), whereas inhibition of p38 and mitogen-activated protein\/extracellular signal-regulated kinase did not effect survival. ELISA revealed that these cultures contained TNF\u03b1, and exposure to an anti-TNF\u03b1 antibody inhibited NF-\u03baB DNA-binding activity by \u223c35% and killed \u223c40% of medium to large neurons within 24 h. The results show for the first time that cytokine-mediated activation of NF-\u03baB is a component of the signaling pathway responsible for maintenance of adult sensory neuron survival after axon damage.<\/jats:p>","DOI":"10.1523\/jneurosci.3127-04.2005","type":"journal-article","created":{"date-parts":[[2005,2,16]],"date-time":"2005-02-16T20:58:29Z","timestamp":1108587509000},"page":"1682-1690","source":"Crossref","is-referenced-by-count":79,"title":["Activation of Nuclear Factor-\u03baB via Endogenous Tumor Necrosis Factor \u03b1 Regulates Survival of Axotomized Adult Sensory Neurons"],"prefix":"10.1523","volume":"25","author":[{"given":"Paul","family":"Fernyhough","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrell 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