Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke.

Article (PDF Available)inBrain research 1514 · January 2013with49 Reads
DOI: 10.1016/j.brainres.2013.01.023 · Source: PubMed
  • 32.92 · University of North Texas HSC at Fort Worth
  • 38.11 · University of North Texas HSC at Fort Worth
The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the "critical period" and newly emerged "biomarkers window" hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials.

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    • "is started, the type and possibly the scheduling of hormone treatment (Villa et al., 2016 ). Detrimental effects of hormone treatment on heart attack, stroke or deep vein thrombosis may be due to pro-thrombotic actions of estrogens in individuals with acute disruption of atherosclerotic plaques (Liu and Yang, 2013). The main obstacle to study the effects and design suitable hormone therapies is the fact that estrogens do not seem to play a primary role as promoters of the neurodegenerative program but participate only in the complex combination of events that trigger neurodegeneration . "
    [Show abstract] [Hide abstract] ABSTRACT: Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases. Then, restoring neuroendocrine axes during aging can be key to enhance brain health through neuroprotection and neuroregeneration, depending on the modulation of plasticity mechanisms. Estrogen-dependent transient receptor potential cation channel, subfamily V, member 1 (TRPV1) expression induces neuroprotection, neurogenesis and regeneration on damaged tissues. Agonists of TRPV1 can modulate neuroprotection and repair of sensitive neurons, while modulators as other cognitive enhancers may improve the survival rate, differentiation and integration of neural stem cell progenitors in functional neural network. Menopause constitutes a relevant clinical model of steroidal production decline associated with progressive cognitive and mental impairment, which allows exploring the effects of hormone therapy in health outcomes such as dysfunction of CNS. Simulating the administration of hormone therapy to virtual menopausal individuals allows assessing its hypothetical impact and sensitivity to conditions that modify the effectiveness and efficiency.
    Full-text · Article · Sep 2016
    • "Some researchers have found a lower incidence of stroke in pre-menopausal women, but a higher incidence of stroke in post-menopausal women compared with men. This phenomenon may be due to the potential neuroprotective benefits of hormones, most notably estrogen [15,16]. However, estrogen had no dominant effects in female patients with AF. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Chinese herbal products (CHPs) are widely used for atrial fibrillation (AF) in Taiwan. We investigated the effect of adjuvant CHPs in preventing ischemic stroke in patients with AF. Methods: Taiwanese patients in the Health Insurance Database newly diagnosed with AF during 2000-2011 were enrolled. Medication treatment with/without CHPs was administered within 7 days after the AF diagnosis. The clinical endpoint was an ischemic stroke. The Chi-square test, Fisher's exact test, and Student t test were used to examine differences between the traditional Chinese medicine (TCM) and non-TCM cohorts. Cox proportional hazard regression was used to assess the risk for ischemic stroke between two cohorts. Results: Three hundred and eleven patients underwent TCM treatment and 1715 patients did not. Compared to non-TCM users, TCM users had a lower incidence of stroke (12.59% vs. 1.93%, respectively) and lower risk of stroke [CHA2DS2-VASc score = 0-2 (hazard ratio = 0.20; 95% confidence interval = 0.06-0.65)]. Compared to non-TCM users, the stroke risk was significantly lower in TCM users with AF who were female or younger than 65 years, but not in males, people more than 65 years old, or people with comorbidities. Compared to TCM users, non-TCM users who received conventional treatment had a higher ischemic stroke risk. The risk for AF-related hospitalization was significantly lower in TCM users (0.64%) than in non-TCM users (38.1%). Conclusions: Users of TCM with AF have a lower risk of new-onset ischemic stroke. Therefore, adjuvant CHP therapy may have a protective effect and may be used in AF patients to prevent ischemic stroke.
    Full-text · Article · Jul 2016
    • "There has been an increasing interest in using estrogens after the onset of ischemic stroke, alone or in combination with other strategies, to promote neuroprotection and functional recovery (reviews by Liu and Yang (2013), Schreihofer and Ma (2013)). In the current study, E2 treatment was able to remarkably decrease lesion volume and accelerate recovery of forelimb function when administered at the time of reperfusion in an experimental stroke model in rats. "
    [Show abstract] [Hide abstract] ABSTRACT: Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke.
    Full-text · Article · Mar 2016
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