Chronic 17β-estradiol pretreatment and ischemia-induced hippocampal degeneration and memory impairments: A 6-month survival study

Acute pretreatment with estradiol protects against CA1 cell loss and spatial learning impairments resulting from transient global ischemia

“…Gulinello and colleagues (2006) recently reported that both chronic pretreatment with physiologic levels of estradiol as well as acute administration of high levels estradiol directly to the brain immediately following ischemia yield significant protection against impairments in visual and spatial working memory assessed with an object recognition task and an object placement task. Most recently, 15 days of estradiol treatment prior to ischemia has been shown to yield long lasting protection from ischemia-induced deficits in performance on an object recognition task and deficits in reference memory assessed with a radial arm maze (Plamondon et al, 2006). Unlike these studies which utilized either multiple weeks of estradiol prior to ischemia (Gulinello et al, 2006;Kondo et al, 1997;Plamondon et al, 2006) or one high pharmacological dose administered directly to the brain (Gulinello et al, 2006), we administered two acute injections of estradiol 48 and 24 hrs prior to ischemia.…”

“…Most recently, 15 days of estradiol treatment prior to ischemia has been shown to yield long lasting protection from ischemia-induced deficits in performance on an object recognition task and deficits in reference memory assessed with a radial arm maze (Plamondon et al, 2006). Unlike these studies which utilized either multiple weeks of estradiol prior to ischemia (Gulinello et al, 2006;Kondo et al, 1997;Plamondon et al, 2006) or one high pharmacological dose administered directly to the brain (Gulinello et al, 2006), we administered two acute injections of estradiol 48 and 24 hrs prior to ischemia. This pattern of hormone administration likely resulted in circulating levels of estradiol that were in the high physiological range at the time of ischemia (Woolley and McEwen, 1993).…”

“…Transient global ischemia results in severe impairments in performance on hippocampally-dependent spatial learning tasks such as the Morris water maze (Block and Schwarz, 1997,1998;Hagan and Beaughard, 1990;Jaspers et al, 1990;Nelson et al, 1997;Nunn et al, 1994;Olsen et al, 1994;Wright et al, 1996). Ischemia also leads to deficits in working memory as assessed with object and place recognition tasks (Gulinello et al, 2006;Mumby et al, 1996;Plamondon et al, 2006;Wood et al, 1993). While some studies suggest that the magnitude of hippocampal damage resulting from transient global ischemia is correlated with performance on learning and memory tasks (e.g., Kiyota et al, 1991;Olsen et al, 1994), others have reported no correlation between these neural and behavioral measures (Kondo et al, 1997;Nunn et al, 1994).…”

Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

“…A number of studies also examined estrogen effect upon cerebral blood flow and showed it had little or no significant effect, implying that the neuroprotective effect of estrogen occurs directly at the level of the brain. The neuroprotective effect of estrogen in global cerebral ischemia, which affects primarily the CA1 region of the hippocampus, was shown to be correlated with significant improvements in recognition, working memory and spatial memory [30][31][32]. Likewise, the sensorimotor deficits observed in MCAO have been reported to be significantly reduced by estradiol treatment, an effect that correlated with estrogen reduction of infarct size [33].…”

“…Several studies have shown that a 24h pretreatment and enhanced gene expression is needed to observe the protective effects of estrogen in cerebral ischemia [24,32,45], although there are dissenting reports in the literature [31,46,47]. Several groups have thus explored the potential role of estrogen receptors in mediation of the neuroprotective effects of estrogen.…”