parallel increases in TNF-α in the blood and brain (Qin et al. 2007). In transgenic mice lacking TNF receptors, however, LPS increased TNF-α only in the blood but not in the brain, suggesting that LPS–TLR4 induction of TNF-α in the blood leads to TNF transport by its receptors across the BBB and activation of proinflammatory responses in the brain. Transgenic mice without the TNF-α receptor cannot transport the cytokine to the brain; consequently, the LPS–TLR4 proinflammatory response is amplified across peripheral tissues but does not spread to the brain.
