A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke

Abstract

Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. Adult female Sprague-Dawley rats were ovariectomized and fed either an isoflavone-reduced diet (IFP) or a high soy diet (SP) for 2 weeks before undergoing 90 min of transient middle cerebral artery occlusion (tMCAO) followed by 22.5 h reperfusion. Infarct size, as assessed by triphenyltetrazolium chloride staining, was significantly reduced by a high soy diet (P<0.05). Apoptosis in the ischemic cortex, measured by TUNEL staining, was significantly reduced by the high soy diet. The number of active caspase-3 positive cells and caspase-mediated alpha-spectrin cleavage were also significantly decreased in the ischemic cortex of SP rats. Furthermore, nuclear translocation of apoptosis-inducing factor (AIF) was significantly reduced in the ischemic cortex of SP rats. Soy significantly increased bcl-x(L) mRNA and protein expression in the ischemic cortex compared with IFP rats. Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-x(L) in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-x(L) following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex.

Effects of Soybean Isoflavone on the Notch Signal Pathway of the Brain in Rats with Cerebral Ischemia

“…Dietary isoflavones have been shown in rats to improve stroke outcome after transient focal cerebral ischemia, as indicated by smaller infarct volume and improved neurological status ( 3 ). A decrease in apoptotic rate in the cerebral cortex accompanies the decrease in brain infarct size conferred by a soybeanenriched diet in rats subjected to MCAO ( 6 ). In vitro experiments have confirmed that apoptosis is a potential target of soybean isoflavones, because genistein prevents glutamate-and thapsigargin-induced apoptosis in embryonic cerebral cortical cell cultures ( 15 -17 ).…”

“…Dietary soybean, which is rich in isoflavaones, decreases stroke injury in both female and male rats ( 4 ) and the soybean isoflavone genistein confers neuroprotection in a mouse cerebral ischemia model ( 5 ). Importantly, dietary supplementation with soybean decreases apoptotic rate in the cerebral cortex of rats subjected to MCAO ( 6 ). However, the molecular mechanisms underlying these beneficial effects of isoflavones in the central nervous system are unknown ( 7 , 8 ).…”

Can Soy Diet be Protective in Severe and Diffuse Traumatic Brain Injury?

“…The improvement of neurologic outcome by genistein has been reported in a model of ischemia in mice [54]. The isoflavones of dietary soy have improved stroke outcome in male rats following ischemia [20,[55][56][57]. The increase in neurologic score can occur through ICP decrease [25,28].…”

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

“…Both ovariectomized female and male rats on a high soy diet show a significant reduction in infarct size, neurological deficit, and cerebral apoptosis following transient or permanent middle cerebral artery occlusion (Schreihofer et al, 2005;Burguete et al, 2006;Lovekamp-Swan et al, 2007a;Castello-Ruiz et al, 2011). The addition of the soy isoflavones genistein or equol to the diet has similar protective effects in both sexes (Ma et al, 2010;Castello-Ruiz et al, 2011;Qian et al, 2012).…”

“…Because soy isoflavones have properties of phytoestrogens and can bind and activate estrogen receptors, these protective effects are likely to include those implicated in estrogen-dependent neuroprotection. Like estrogens (Dubal et al, 1999;Alkayed et al, 2001;Won et al, 2006), dietary soy isoflavones enhance the expression of antiapoptotic members and inhibit pro-apoptotic members of the Bcl-2 family of proteins (Bu and Lephart, 2005;Lovekamp-Swan et al, 2007a). Similarly, both estrogens (Razmara et al, 2008;Zhang et al, 2009) and soy isoflavones (Ma et al, 2010(Ma et al, , 2013Qian et al, 2012) reduce oxidative stress in response to cerebral ischemia.…”