Activation of the NF-κB spreads through positive loops (Fig. 2) increasing activation within and across glia and neurons (Zou and Crews 2010). Autocrine signaling involves secretion of signaling molecules that act on the same cells receptors to amplify activation of that cell, whereas paracrine signaling involves release of signals that activate cells nearby spreading the signal across cells. For example, reactive oxygen species (ROS) can increase NF-κB transcription of TNFα and TACE, the TNFα activating protease, as well as the TNFR1 receptor. Released TNFα stimulates NF-κB transcription through TNFR1 amplifying the signal in that cell and adjacent cells promoting TNFα induction (Fig. 2). Stress and drugs acutely signal through brain NF-κB. For example, restraint stress in rats induces brain NF-κB target genes TACE and TNFα mRNA within 30 minutes, and free mature brain TNFα within 1 hour (Madrigal et al. 2002). Similarly an acute dose of ethanol activates NF-κB in brain within 30 minutes (Ward et al. 1996). Although NF-κB is expressed in most cells, in brain NF-κB is transcriptionally active primarily in glia (Mao et al. 2009), although, confusion
