Other studies suggest that endotoxemia leads to inflammation in brain, with alteration in BBB, up-regulation of aquaporin 4 (AQP4) and associated edema, neutrophil infiltration, astrocyte activation, as well as apoptotic cell death, all of which appear to be mediated by TNF-alpha signaling through TNF-receptor 1 [28]. This evidence concerns the gene AQP4 and serum lipopolysaccharide activity.