Revisiting the timing hypothesis: biomarkers that define the therapeutic window of estrogen for stroke.

Revisiting the timing hypothesis: biomarkers that define the therapeutic window of estrogen for stroke.
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DOI:
10.1016/j.yhbeh.2012.06.002
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发表时间:
2013-02
影响因子:
3.5
通讯作者:
Balden, Robyn
Balden, Robyn
中科院分区:
医学3区
文献类型:
--
作者:
Sohrabji, Farida;Selvamani, Amutha;Balden, Robyn

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Significantly extended life expectancy coupled with contemporary sedentary lifestyles and poor nutrition have created a global epidemic of cardiovascular disease and stroke. For women, this issue is complicated by the discrepant outcomes of hormone therapy (HT) for stroke incidence and severity as well as the therapeutic complications for stroke associated with advancing age. Here we propose that the impact of estrogen therapy cannot be considered in isolation, but should include age-related changes in endocrine, immune, and nucleic acid mediators that collaborate with estrogen to produce neuroprotective effects commonly seen in younger, healthier demographics. Due to their role as modulators of ischemic cell death, the post-stroke inflammatory response, and neuronal survival and regeneration, this review proposes that Insulin-like Growth Factor (IGF)-1, Vitamin D, and discrete members of the family of non-coding RNA peptides called microRNAs (miRNAs) may be crucial biochemical markers that help determine the neuroprotective “window” of HT. Specifically, IGF-1 confers neuroprotection in concert with, and independently of, estrogen and failure of the insulin/IGF-1 axis is associated with metabolic disturbances that increase the risk for stroke. Vitamin D and miRNAs regulate and complement IGF-1 mediated function and neuroprotective efficacy via modulation of IGF-1 availability and neural stem cell and immune cell proliferation, differentiaton and secretions. Together, age-related decline of these factors differentially affects stroke risk, severity, and outcome, and may provide a novel therapeutic adjunct to traditional HT practices.
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