TNF and Sepsis: Alexander et al. found that after intraperitoneal injection of LPS of E. coli O55:B55, the concentration of TNF-α, a key metabolic mediator in sepsis in the blood, increased significantly after 1 hour’s treatment, which resulted in a decrease in the integrity of BBB, infiltration of neutrophils into the brain and the subsequent SAE symptoms (Alexander et al., 2008).