Abstract TP207: Effects Of Dietary Genistein And Estrogen On Post-stroke Inflammation: Relation To Age And Length Of Estrogen Deprivation.

Background: Poststroke inflammation plays an important role in the pathophysiology and prognosis of ischemic stroke. Preclinical investigations with the soy-derived phytoestrogen genistein have shown neuroprotective effects under conditions of brain ischemia. However, little is known about how endogenous estrogen deprivation and age influence the neuroprotection of genistein following focal cerebral ischemia. In this study, we investigated the effects of dietary genistein (Gen) on chronic poststroke inflammation and the probable mechanisms underlying its inflammatory responses after hypogonadism. Method: Young adult (~3-4 months) and proven retired breeder middle-aged Sprague-Dawley rats (~9 months) were used in the study. Rats were ovariectomized and randomly assigned to different durations of hypogonadism (2 vs 12 wks) followed by a two-wk pretreatment with Gen or 17β-estradiol (E2) implant before inducing 60 min. middle cerebral artery occlusion. After 21 days post-ischemia reperfusion, brains were harvested and processed for biochemical analyses to determine the effect of Gen and E2 on the Interleukin-6 (IL-6) and Transforming Growth Factor (TGF-β1) as surrogate markers of M1 and M2 activation respectively. GAP43 was further investigated as a marker of functional recovery. Results: Although there were no significant effects in the ischemic hemisphere, Gen treatment reduced IL-6 expression in the contralateral hemisphere in young subjects while E2 did not affect IL-6 across lengths of hypogonadism in the young cohort (p%lt0.05). After short-term estrogen deprivation, E2 and Gen increased TGF-β1 at the contralateral hemisphere in both young rats and middle-aged rats (p%lt0.05). Gen but not E2 increased GAP43 at the contralateral hemisphere of the young following short-term hypogonadism (p%lt0.05). Conclusion: Our results show that Gen reduces contralateral M1 activation in young ovariectomized rat brains independent of the length of estrogen deprivation after focal cerebral ischemia. Both Gen and E2 differentially promote M2 activation as a function of age but may not influence the inflammatory response in the ischemic hemisphere following extended reperfusion poststroke.