TNF and Encephalopathy: Indeed, TNF-α is a key mediator of septic encephalopathy, as TNF-α-deficient mice are resistant to LPS-induced encephalopathy [37,38] and TNF-α might activate the TNF-related apoptosis-inducing ligand (TRAIL) receptor leading to cell apoptosis on neurons, astrocytes, and oligodendrocytes [39].