Differential neuroprotection of selective estrogen receptor agonists against autonomic dysfunction and ischemic cell death in permanent versus reperfusion injury

Abstract

In the present study, we tested the hypothesis that selective activation of estrogen receptor subtypes (ER and ER) would be neuroprotective following ischemia and/or ischemia-reperfusion, as well as prevent the associated autonomic dysfunction. The selective ER agonist, PPT, when administered 30min prior to occlusion of the middle cerebral artery (pMCAO), resulted in a dose-dependent neuroprotection as measured 6 hours postpermanent MCAO, but not following 30mins of MCAO followed by 5.5hrs of reperfusion (I/R). In contrast, 30min pretreatment with the selective ER agonist, DPN, resulted in a dose-dependent neuroprotection following I/R, but was not protective following pMCAO. Both drugs prevented the ischemia-induced autonomic dysfunction as measured by a decrease in the baroreceptor reflex sensitivity (BRS). The data presented here suggest a differential role of each ER subtype in targeting the mechanisms of cell death that occur in ischemia versus reperfusion injury. Copyright © 2011 Barry J. Connell and Tarek M. Saleh.