Estrogen attenuates tumor necrosis factor-alpha expression to provide ischemic neuroprotection in female rats.

Proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of neurodegenerative diseases including ischemia. Circulating estrogen is positively associated with neuroprotection against ischemia in female rats. In the present study, we examined whether endogenous estrogen levels affect ischemia-induced TNF-alpha expression in normal cycling female rats. An elevated concentration of TNF-alpha was toxic to neurons. A high level of expression of TNF-alpha accompanied the decline in circulating estrogen levels in normal cycling female rats. Estrogen administration attenuated endotoxin-induced TNF-alpha expression and neuronal injury, indicating that the down-regulation of TNF-alpha expression plays a role in ischemic neuroprotection by estrogen. Therefore, we propose that one mechanism by which estrogen protects females from ischemic damage is through the regulation of TNF-alpha production.