Aim: 

We have assessed the hypothesis that: (1) soy-derived isoflavones contained in current laboratory rodent diets improve stroke outcome in female rats; and (2) the pure isoflavone genistein can mimick such a neuroprotective effect.

Methods: 

(1) To determine the effect of dietary isoflavones, non-ovariectomized female Wistar rats were subdivided in two groups: one fed with a soy-based diet and the other with a natural isoflavone-free diet. (2) The acute effects of genistein were studied in ovariectomized and non-ovariectomized rats fed with a synthetic isoflavone-free diet. Transient focal cerebral ischemia (90 min.) was induced by middle cerebral artery occlusion following the intraluminal thread technique, and monitorized by a laser-Doppler probe on the dorsal cortex. A dose of genistein of 1 mg/kg (i.p.) was administered 30 min. after reperfusion, and maintained during 3 days (Alzet osmotic pump, i.p). Neurological examination and cerebral infarct volume measurements were carried out 3 days after the ischemic insult.

Results: 

(1) The mean total infarct volume was significantly lower in rats fed with the soy-based diet than in rats fed with the isoflavone-free diet (24.94.7%vs 30.35.9% of the total volume of the ispilateral hemisphere, p<0.05). Neurological scores were not significantly different. (2) In non-ovariectomized rats, acute treatment with genistein reduced the mean total infarct volume from 26.87.4% to 13.77.4%, although such a difference was not statistically significant. By contrast, neurological score was significantly lower for genistein-treated rats. Neither infarct volume nor neurological score were statistically different between ovariectomized control and genistein-treated rats.

Conclusion: 

Our results lend support to the potential neuroprotective effect of isoflavones in ischemic stroke.

Partially supported by grants PI06/0981 and RD06/0026/0006 (RENEVAS), Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III.