Central inflammatory response to experimental stroke is inhibited by a neuroprotective dose of dietary soy

Dietary soy and soy isoflavones are neuroprotective in experimental cerebral ischemia. Because the isoflavones in soy that are responsible for this neuroprotective effect act as phytoestrogens, we hypothesized that they would mimic the beneficial effects of estrogens on the innate inflammatory response to cerebral ischemia. Ovariectomized Sprague-Dawley rats were fed a soy free diet or a diet containing high dietary levels of soy for 5 weeks, after which they were subjected to transient middle cerebral artery occlusion (tMCAO) for 90 min. Dietary soy was associated with a reduced inflammatory response in the cerebral cortex during the acute innate period 4 and 24 h after tMCAO, including significant (>2-fold) reductions in interleukins 1 beta, 2, and 13, and the chemokine CXCL1. However, there was no effect of soy on tumor necrosis factor-alpha or interferon-gamma. Dietary soy was also associated with a 40 percent reduction in the nuclear translocation of p65 nuclear factor kappa B despite an increase in the expression of p65 RELA mRNA. In support of an early effect on the innate immune response to stroke, soy-fed rats had 44 percent fewer activated microglia in the infarct core than soy free rats. Interestingly, despite increased expression following injury, the steady state mRNA levels of inflammatory factors were not altered in soy-fed rats even though inflammatory proteins were. These data suggest that dietary soy isoflavones, like estrogens, inhibit of the innate immune response to injury. However, post-transcriptional mechanisms may play an important role in the mechanism of this action. Coupled with previously published data, these results support an early and rapid effect of dietary soy on the evolution of brain injury following stroke.