Postischemic Cerebral Blood Flow Recovery in the Female: Effect of 17β-Estradiol

Abstract

Summary: Female reproductive hormones are consid ered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17J3-estradiol is impor tant to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 1713-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 ± 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 ± 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (micro spheres) and somatosensory evoked potential (SEP) am plitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distri-The incidence of atherosclerotic vascular disease in premenopausal women is less than in men, but this difference disappears after menopause (Bush and Miller, 1987; Wolf et aI., 1987; Barrett-Connor and Bush, 199 1; Sivenius et aI. , 199 1). These obser vations have historically been interpreted as evi dence that female reproductive hormones confer vascular protection in ischemic heart disease and stroke. However, it is unclear if estrogen per se is critical to stroke risk or by what mechanism protec tion is achieved. Further, the presence of vascular responses unique to the female in an ongoing cere- 666bution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 ± 1 and 9 ± 2 ml min -I 100 g-I, respectively); however postischemic hyperemia was greater in FEM than M (CBF = 25 7 ± 27 and 18 3 ± 27 ml min -1 100 g -I. However, EFEM experienced higher CBF during ischemia (e.g., 13 ± 2ml min-1100 g-l) and less hyperemia (134 ± 4 ml min -I 100 g-I in hemi spheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recov ery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17J3-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal.

Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice

“…Estrogen exerts many diverse cellular effects in neural tissue, including acting as a neurotrophic factor during the processes of cell proliferation and differentiation. Estrogen also exerts neuroprotective effects in pathological environments, including glutamate excitotoxicity [26], oxidative stress [27,28], β-amyloid-induced toxicity [26], neurotoxin treatment [29], cerebral ischemia [30][31][32], forebrain transections [33], excitotoxin-induced forebrain injury [34][35][36], Alzheimer's disease [37][38][39], and Parkinson's disease [40].…”

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…In particular, several investigators have examined the efficacy of 17␤-estradiol in models of stroke (Alkayed et al, 1998aCarswell et al, 2004;Dubal et al, 1998;Fukuda et al, 2000;Hurn et al, 1995;McCullough et al, 2001;Toung et al, 1998;Yang et al, 2000). Hurn and colleagues (1995) first described in a model of global cerebral ischemia the effects of chronic 17␤-estradiol treatment.…”

“…These include cerebral blood flow (Alkayed et al, 1998a;Hurn et al, 1995;Roof and Hall, 2001), leukocyte adhesion (Santizo et al, 2000), edema formation (Roof et al, 1992;Roof et al, 1993;Roof et al, 1994), antioxidant production (Ayres et al, 1998;BruceKeller et al, 2000;Culmsee et al, 1999;Sawada et al, 1998), inflammation Ray et al, 1997;Salem et al, 2000;St Clair, 1997;Vegeto et al, 2001), excitotoxicity (Singer et al, 1996;Smith et al, 1987;Weaver et al, 1997), apoptosis (Alkayed et al, 1998b;Alkayed et al, 2001), ␤ amyloid (Goodman et al, 1996;Shi et al, 1998), and growth factor regulation (Gollapudi and Oblinger, 1999;Toran-Allerand, 1996). Hormones have the ability to target multiple pathways that are involved in injury.…”

Neuroprotection in Animal Models of Global Cerebral Ischemia

“…Besides, the opportunity time window may be further extended when it is expected that neuroprotective procedures act through promotion of cellular processes of neuronal repair and plasticity. In view of the multiple pathophysiological processes occurring both in sequence and simultaneously after ischemia and reperfusion, it is considered as an advantage for presumptive neuroprotective drugs to have multiple cellular or molecular mechanisms of action, as occurring with some originally endogenous compounds, namely melatonin, estradiol and progesterone (El-Abhar et al, 2002;Hurn et al, 1995;Jover-Mengual et al, 2010;Lebesgue et al, 2009;Reiter et al, 2005;Wang et al, 2008). By contrast, most synthetic drugs only have one mechanism of action accounting for neuroprotection.…”