TNF and central nervous system disorder: It is important to note that TLR4 can activate the downstream signaling pathways, which are strongly correlated with the development of CNS disorders, such as the myeloid differentiation primary response 88- (MyD88-) dependent and the NF-κB signaling pathways; these pathways can trigger and aggravate the inflammatory response releasing various proinflammatory cytokines and mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), cyclooxygenase-2, inducible nitric oxide synthase (iNOS), and the subsequent generation of nitric oxide (NO) [15].