Background: Previous research in animal seizure models indicates that the pleiotropic cytokine TNF is an important effector/mediator of neuroinflammation and cell death. Recently, it has been demonstrated that TNF downregulates Klotho (KL) through the nuclear factor kappa B (NFkB) system in animal models of chronic kidney disease and colitis. KL function in the brain is unclear, although Klotho knockout (Kl-/-) mice exhibit neural degeneration and a reduction of hippocampal synapses.
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