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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin (IL)-1beta is a potent inducer of inflammatory prostaglandins, which are important mediators of vascular response to cerebral injury, whereas estrogen reduces brain injury in models of ischemic stroke. Thus we examined the effects of in vivo IL-1beta exposure on cerebrovascular cyclooxygenase (COX)-2 expression and function in an animal model of chronic estrogen replacement. Estrogen-treated and nontreated ovariectomized female rats received IL-1beta injections (10 microg/kg i.p.), and then cerebral vessels were isolated for biochemical and contractile measurements. In estrogen-deficient rats, IL-1beta induced cerebrovascular COX-2 protein expression; a peak response occurred 3 h after injection. COX-2 was localized to arterial endothelium using confocal microscopy. IL-1beta increased PGE2 but not PGI2 production and decreased vascular tone as measured in isolated cerebral arteries; the latter effect was partially reversed by treatment with the selective COX-2 inhibitor NS-398 (10 micromol/l). In contrast, in animals treated with estrogen, IL-1beta had no significant effect on COX-2 protein levels, PGE2 production, or vascular tone. Combined treatment with 17beta-estradiol and medroxyprogesterone acetate also prevented increases in PGE2 production after IL-1beta treatment, but treatment with 17alpha-estradiol had no effect. IL-1beta induction of COX-2 protein was prevented by treatment with the nuclear factor-kappaB inhibitor caffeic acid phenethyl ester (20 mg/kg i.p.), and estrogen treatment reduced cerebrovascular nuclear factor-kappaB activity. Estrogen thus has potent anti-inflammatory effects with respect to cerebral vascular responses to IL-1beta. These effects may have important implications for the incidence and severity of cerebrovascular disease.
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PMID:Estrogen suppresses IL-1beta-mediated induction of COX-2 pathway in rat cerebral blood vessels. 1468 67

Diabetic hyperglycemia increases ischemic brain damage in experimental animals and humans. The mechanisms are unclear but may involve enhanced apoptosis in penumbral regions. Estrogen is an established neuroprotectant in experimental stroke. Our previous study demonstrated that female diabetic db/db mice suffered less damage following cerebral hypoxia-ischemia (H/I) than male db/db mice. Here we investigated the effects of diabetes and estrogen apoptotic gene expression following H/I. Female db/db and nondiabetic (+/?) mice were ovariectomized (OVX) and treated with estrogen or vehicle prior to H/I; brains were analyzed for damage and bcl-2 family gene expression. OVX increased ischemic damage in +/? mice; estrogen reduced tissue injury and enhanced antiapoptotic gene expression (bcl-2 and bfl-1). db/db mice demonstrated more damage, without increased bcl-2 mRNA; bfl-1 expression appeared at 48 hours of recovery associated with infarction. To our knowledge, this is the first description of bfl-1 in the brain with localization to microglia and macrophages. Early induction of bfl-1 expression in +/? mouse brain was associated with microglia; delayed bfl-1 expression in diabetic brain was in macrophages bordering the infarct. Furthermore, estrogen replacement stimulated early postischemic expression of bcl-2 and bfl-1 and reduced damage in normoglycemic animals but failed to protect the diabetic brain.
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PMID:Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice. 1470 12

Estrogen has been demonstrated to protect against brain injury, neurodegeneration, and cognitive decline. Furthermore, estrogen seems to specifically protect cortical and hippocampal neurons from ischemic injury. Here our data evaluating the neuroprotective effects of estrogens, the selective estrogen receptor modulators (SERMs), and estrogen receptor alpha- and beta-selective ligands in animal models of ischemic injury are discussed. In rats and mice, the middle cerebral artery occlusion (MCAO) model was used as models representing cerebrovascular stroke, while in gerbils the two-vessel occlusion model, resenting acute heart attack, was used. Using focal ischemia in ovariectomized ERalphaKO, ERbetaKO, and wild-type mice, we clearly established that the ERalpha subtype is the critical ER-mediating neuroprotection in mouse focal ischemia. Because of the characteristic blood supply of the gerbil, the gerbil global ischemia model was used to evaluate the neuroprotective effects of estrogen, SERMs, and ERalpha- and ERbeta-selective compounds in the hippocampus. Analysis of neurogranin mRNA, a marker of viability of hippocampal neurons, with in situ hybridization, revealed that estrogen treatment resulted in a complete protection in the CA1 regions not only when administered before, but also when given 1 hour after occlusion. Our in vivo binding studies with (125)I-estrogen in gerbils revealed the presence of nuclear estrogen binding sites primarily in CA1 neurons, but not in the CA3 region, as we saw in rats and mice. Together, these observations demonstrate that estrogen protects from ischemic injury in both the focal and global ischemia models by acting primarily via classical nuclear receptors.
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PMID:Neuroprotection by estrogen in animal models of global and focal ischemia. 1499 43

Renal insufficiency is a risk factor for coronary heart disease and stroke, but whether it predicts lower extremity peripheral arterial disease (PAD) is unknown. The authors evaluated was the association of baseline renal insufficiency with future PAD events in the Heart and Estrogen/Progestin Replacement Study (HERS) and follow-up study (HERS II). A total of 2763 postmenopausal women with known coronary heart disease were enrolled in HERS and randomly assigned to receive hormone therapy with conjugated estrogens and medroxyprogesterone acetate or placebo and followed for up to 8 yr for clinical end points. The outcome was time from randomization to first occurrence of either a lower extremity amputation, revascularization (surgical or percutaneous), or lumbar sympathectomy during follow-up. Incident lower extremity PAD event rates among women with creatinine clearances > or =60, 30 to 59, and < 30 ml/min/1.73 m(2) were, respectively, 0.55%, 0.92%, and 2.73% per year. After multivariable proportional-hazard adjustment for potential confounders and other known risk factors for PAD, women with a creatinine clearance 30 to 59 ml/min/1.73 m(2) (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.04 to 2.54, P = 0.032) and <30 ml/min/1.73 m(2) (HR, 3.24; 95% CI, 1.20 to 8.78, P = 0.021) had a significantly increased risk of PAD compared with participants with a creatinine clearance > or =60 ml/min/1.73 m(2). Renal insufficiency was independently associated with future PAD events among postmenopausal women with coronary heart disease. Future studies should determine whether this association is present in other populations and investigate its potential mechanisms.
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PMID:Renal insufficiency and the risk of lower extremity peripheral arterial disease: results from the Heart and Estrogen/Progestin Replacement Study (HERS). 1503 8

The authors investigated the relationship between statin use and the risk of stroke in the Heart and Estrogen-Progestin Replacement Study (HERS). Despite large reductions in relative risk point estimates, statin use was not associated with differences in the risks of all fatal stroke (relative hazard [RH] 0.52, 95% CI 0.23 to 1.18, p = 0.12), fatal ischemic stroke (RH 0.51, 95% CI 0.18 to 1.45, p = 0.21), fatal hemorrhagic stroke (RH 0.18, 95% CI 0.02 to 1.46, p = 0.11), or TIA (RH 1.32, 95% CI 0.84 to 2.09, p = 0.23).
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PMID:Statin use and stroke outcomes in the Heart and Estrogen-Progestin Replacement Study (HERS). 1503 2

While most women will suffer from hot flashes at some point over their lifetime, most symptoms resolve with time. However, some women may experience severe and/or long-lasting hot flashes. Estrogen, the most effective treatment for hot flashes, is not generally recommended for women with a history of breast cancer or women at high risk of developing breast cancer. Moreover, long-term administration of estrogen to healthy women is associated with increased risks of cardiovascular disease, stroke, and breast cancer. Newer antidepressants from the selective serotonin or noradrenergic reuptake inhibitor family, such as venlafaxine and paroxetine, appear to be among the most effective nonhormonal agents for the treatment of hot flashes. New information demonstrates that gabapentin also is an effective nonhormonal therapy for hot flashes. In this review, we will discuss current knowledge of the epidemiology and pathophysiology of hot flashes, along with treatment options. We will focus on nonhormonal treatments that have been studied in prospective randomized clinical trials, and will present an algorithm for the treatment of symptomatic patients.
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PMID:New therapeutic approaches for hot flashes in women. 1535 39

Elevation of extracellular levels of amino acids has been implicated in the pathogenesis of stroke. The failure of brain energy metabolism due to the lack of oxygen and glucose contributes also to cell loss. Estrogen has been shown to protect brain cells against ischemia by a still unclear mechanism. We used intracerebral microdialysis to monitor the effects of acute 17beta-estradiol treatment on the release of glutamate and aspartate and on the levels of the energy metabolites glucose and lactate. In male rats subjected to 90 min of transient middle cerebral artery occlusion followed by 24-h reperfusion, acute treatment with 17beta-estradiol (0.8 mg/kg, i.v.) at the time of occlusion reduced the ischemic infarct by about 50%. In these treated rats, the ischemia-induced increases of extracellular levels of glutamate and aspartate were significantly and rapidly reduced. The reduction of glucose level during occlusion was not affected by 17beta-estradiol treatment; however, the increase of extracellular lactate was reduced during occlusion and reperfusion, probably due to the reduced glutamate-driven astrocytic glycolysis. These data suggest that acute treatment with 17beta-estradiol at the onset of occlusion significantly reduces the ischemia-induced excitotoxicity in the cortex, a mechanism that may participate in the neuroprotective effect on cellular survival.
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PMID:Acute effects of 17beta-estradiol on the extracellular concentration of excitatory amino acids and energy metabolites during transient cerebral ischemia in male rats. 1535 25

Bench research suggests that postmenopausal hormonal therapy is associated with beneficial effects on the brain and vascular system. Observational data suggest that postmenopausal hormone replacement therapy is associated with a 25% to 50% lower rate of cardiovascular disease; however, observational data for hormonal therapy is associated with the potential for significant biases. Clinical trial data are needed. There are 3 major clinical trials that inform us about stroke and postmenopausal hormone replacement therapy. Two trials focused on secondary prevention: the Heart and Estrogen/progesterone Replacement Study (HERS) and the Women's Estrogen for Stroke Trial (WEST). One examined primary prevention: the Women's Health Initiative (WHI). All indicate that postmenopausal hormone therapy is not effective for reducing the risk of a recurrent stroke or death among women with established vascular disease or for prevention of a first stroke. Similar results exist for cardiovascular disease. The results of these trials are now reflected in national guidelines. Hormone therapy should not be initiated to prevent vascular disease among postmenopausal women. As a result of these trials, the portion of postmenopausal women using hormone replacement therapy in the United States has fallen by more than half over the past decade.
Stroke 2004 Nov
PMID:Hormone replacement therapy and stroke: clinical trials review. 1545 43

1. The present work discussed the effects of substrain or genetic differences, gender, and age of the rat on infarct size produced by distal middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). 2. In SHR/Kyushu, infarct volume was significantly larger than that of SHR/Izm, while blood pressure levels were essentially the same between the two substrains. Although SHR-SP/Izm had a higher blood pressure than SHR/Kyushu, infarct volumes were the same between SHR/Kyushu and SHR-SP/Izm. These results suggest the presence of blood pressure-independent factors which affect the infarct size after MCAO. 3. Estrogen accounted the large part of greater tolerability against focal brain ischemic injury in female compared with male SHR. 4. We found age-related vulnerability to focal cerebral ischemia in female SHR. This age-related vulnerability in aged female SHR was unrelated to the blood levels of sex hormones such as estrogens and progesterone. 5. Finally, we emphasized the importance of reproducible and least invasive focal ischemia models in stroke research.
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PMID:Substrain differences, gender, and age of spontaneously hypertensive rats critically determine infarct size produced by distal middle cerebral artery occlusion. 1548 33

Recent data from the Women's Health Initiative have highlighted many fundamental issues about the utility and safety of long-term estrogen use in women. Current hormone replacement therapy for postmenopausal women incorporates progestin with estrogen, but it is uncertain if combined therapy provides major cerebrovascular risks or benefits to these women. No experimental animal stroke studies have examined combined hormone administration. The authors tested the hypothesis that combined hormone treatment reduces ischemic injury in middle-aged female rat brain. Reproductively senescent female rats underwent 2-hour middle cerebral artery occlusion (MCAO) followed by 22 hours reperfusion. Estrogen implants were placed subcutaneously at least 7 days before MCAO, and progesterone intraperitoneal injections were given 30 minutes before MCAO, at initiation, and at 6 hours of reperfusion. Rats received no hormone, a 25-microg estrogen implant, a 25-microg estrogen implant plus 5 mg/kg intraperitoneal progesterone, or 5 mg/kg intraperitoneal progesterone. Cortical, caudoputamen, and total infarct volumes were assessed by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis at 22 hours reperfusion. Cortical and total infarct volumes, except in the acute progesterone-treated group, were significantly attenuated in all estrogen-alone and combined hormone-treated groups. There were no significant differences in caudoputamen infarct volumes in all hormone-treated groups as compared with untreated rats. These data have potential clinical implications relative to stroke for postmenopausal women taking combined hormone replacement therapy.
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PMID:Effects of combined estrogen and progesterone on brain infarction in reproductively senescent female rats. 1552 16


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