The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood‐Brain Barrier Permeability

Cipolla, Marilyn J.; Godfrey, Julie A.; Wiegman, Marchien J.

doi:10.3109/10739680903164131

Cited by 48 publications

(26 citation statements)

References 53 publications

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“…The permeability of the BBB may be modulated through both ERα and ERβ (Bake and Sohrabji, 2004; Brown et al, 2010; Cipolla et al, 2009). 17βE2 also plays an important role in mediating leukocyteendothelial interations.…”

Section: Mechanisms Of Estrogen Neuroprotectionmentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

170

121

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There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury.

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Section: Mechanisms Of Estrogen Neuroprotectionmentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

170

121

View full text Add to dashboard Cite

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“…Animal studies also support a role of E2 on EC integrity and permeability. Studies have shown that the permeability of the blood brain barrier is 500% greater in ovariectomized (OVX) than intact female rats, and E2 replacement restores barrier properties [57]. The E2-induced decrease in EC permeability may be related to regulation of prostaglandin E2 (PGE2) levels [58].…”

Section: Introductionmentioning

confidence: 99%

Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

Gencel¹,

Benjamin²,

Bahou³

et al. 2012

MRMC

117

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Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of long-term follow-up. Further investigation of the cellular mechanisms underlying the vascular effects of phytoestrogens and careful evaluation of the epidemiological evidence and clinical trials of their potential vascular benefits would put forward the use of phytoestrogens as an alternative MHT for the relief of menopausal symptoms and amelioration of postmenopausal CVD.

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“…In our study, however, BBB permeability increased significantly in the ovariectomized ischemic group, and this result is different from the results of the above-cited study. In a study by Cipolla et al (8) estrogen treatment to ovariectomized rats was found to significantly lower the permeability of the blood-brain barrier. Chi et al (7) investigated the effect of 17β-estradiol on BBB permeability during focal cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats

Üzüm¹,

Bahçekapılı²,

Baltacı³

et al. 2015

Acta Physiologica Hungarica

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The aim of present study was to determine the effect of estrogen treatment on blood-brain barrier permeability in rats with induced global cerebral ischemia. The study included six-month-old female Sprague-Dawley rats which were divided into the following groups: Control-Ischemia-Reperfusion (C + I-R); Ovariectomy-Ischemia-Reperfusion (Ovx + I-R); Ovariectomy + Estrogen + Ischemia-Reperfusion (Ovx + E + I-R); Ovariectomy + IschemiaReperfusion + Estrogen (Ovx + I-R + E). Ischemia-reperfusion was induced by clamping two carotid arteries, then opening the clamp. Blood-brain barrier permeability was visualized by Evans Blue extravasation and quantified by spectrophotometry. Our results indicate that following ischemia-reperfusion the BBB permeability is increased in ovariectomized rats (Evans Blue extravasation) compared to the control group in the cortex, thalamus, hippocampus, cerebellum and brain stem, while in the midbrain no significant increase was detected. In contrast, BBB permeability in the groups treated with estrogen, administered either before or after ischemia-reperfusion, was significantly lower than in ovariectomized animals. In conclusion, the increase in BBB permeability resulting from experimentally induced cerebral ischemia was prevented by exogenous estrogen treatment. The study results indicate that estrogen may be used for therapeutic purposes in ischemia-reperfusion.

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The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood‐Brain Barrier Permeability

Cited by 48 publications

References 53 publications

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

Pre- and post-estrogen administration in global cerebral ischemia reduces blood-brain barrier breakdown in ovariectomized rats

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