αβκκκκProinflammatory responses expand through paracrine and autocrine amplification, for example, within the initially activated, such as microglia, as well as across adjacent cells through signals that converge upon NF-κB activating transcription [3,50]. TNFα receptors, IL-1β receptors, poly I:C-TLR3 receptors and LPS-TLR4 receptors activate kinases cascades that increase NF-κB transcription [51]. We found increased brain TNFα, IL-1β, IL-6, MCP-1 and NOX mRNA consistent with activation of NF-κB transcription. Resting microglia express TLR and cytokine receptors that can respond to cytokines entering the brain and contribute to proinflammatory amplification in brain. Increases in brain cytokines transported from blood and/or synthesized within brain likely contribute to brain responses (Figure 13).
