Abstract
BackgroundSeveral studies demonstrate that estrogen treatment improves cerebral blood flow in ischemic brain regions of young ovariectomized (OVX) rats. Estrogen receptor-α (ER-α) may mediate estrogen’s beneficial actions via its effects on the cerebral microvasculature. However, estrogen-derived benefit may be attenuated in aged, reproductively senescent (RS) rats. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-α and ER-β.MethodsFisher-344 (n = 37) female rats were randomly divided into the following groups: OVX, OVX CE-treated, RS untreated, and RS CE-treated. After 30 days pretreatment with CE (0.01 mg/kg) rats were subjected to15 min. transient global cerebral ischemia. Non-ischemic naïve, OVX and RS rats were used as controls. Expression of ER-α and ER-β in isolated cortical cerebral microvessels (20 to 100 µm in diameter) was assessed using Western blot and immunohistochemistry techniques.ResultsAge and reproductive status blunted nonischemic ER-α expression in microvessels of OVX rats (0.31±0.05) and RS rats (0.33±0.06) compared to naïve rats (0.45±0.02). Postischemic microvascular expression of ER-α in OVX rats (0.01±0.0) was increased by CE treatment (0.04±0.01). Expression of ER-α in microvessels of RS rats (0.03±0.02) was unaffected by CE treatment (0.01±0.02). Western blot data are presented as a ratio of ER-α or ER-β proteins to β-actin and. Oral CE treatment had no effect on ER-β expression in postischemic microvessels of OVX and RS rats. Statistical analysis was performed by One-Way ANOVA and a Newman-Keuls or Student’s post-hoc test.ConclusionChronic treatment with CE increases ER-α but not ER-β expression in cerebral microvessels of OVX rats. Aging appears to reduce the normal ability of estrogen to increase ER-α expression in postischemic cerebral microvessels.
Highlights
Brain ischemic stroke is a devastating neurologic disease associated with a high mortality rate and long-term disability in survivors [1,2]
Using this method we validated that the proportion of von Willebrand factor (vWF) (300 kDa) in the cerebral microvessel sample was serially increased in samples filtered three times (0.5160.14) versus those filtered once (0.3260.15) and compared to whole-brain homogenates (0.1260.12; Figure 1B)
We first show that estrogen depletion reduces Estrogen receptor-a (ER-a) expression in isolated cortical cerebral microvessels from non-ischemic young rats compared to naıve rats
Summary
Brain ischemic stroke is a devastating neurologic disease associated with a high mortality rate and long-term disability in survivors [1,2]. The susceptibility of late post-menopausal women to stroke increases to a level beyond that of age-matched men [2,3] Data from both human and animal studies show that estrogen replacement therapy improves postischemic cerebral blood flow (CBF) in pre- and perimenopausal females, but the effect is lost with advancing age and prolonged estrogen deficit [2,4]. Such observations have led to the concept that estrogen may act differently on the aging brain [3,5,6,7] or that prolonged estrogen deprivation prior to initiation of estrogen replacement therapy may diminish the potential benefits of hormone therapy on brain rescue after an ischemic event. Our goal was to determine the effects of aging, estrogen deprivation and estrogen repletion with oral conjugated estrogens (CE) on postischemic cerebral microvascular protein expression of ER-a and ER-b
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call