Estrogen Replacement Therapy for Stroke

Cell Medicine

Sandra Acosta¹  Naoki Tajiri¹  Yuji Kaneko¹  Cyrus Tamboli¹  Sarosh Tamboli¹  Cesar V. Borlongan¹  Mibel Pabon¹  Ike De La Pena¹  Paul R. Sanberg¹ 

[1] Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA

关键词: Estrogen;    Stroke;    Replacement therapy;    Estrogen receptor;    Neuroprotection;    Selective estrogen receptor modulators (SERMs);   

DOI  :  10.3727/215517913X672263

学科分类：生物科学（综合）

来源: Cognizant Communication Corporation

【 摘 要 】

Stroke is the third most common cause of death and severe disability among Western populations. Overall, the incidence of stroke is uniformly higher in men than in women. Stroke is rare in women during the reproductive years and rapidly increases after menopause, strongly suggesting that estrogen (E2) plays an important role in the prevention of stroke. Ongoing studies are currently evaluating both the benefits and the risks associated with E2 replacement therapy and hormone replacement therapy in stroke. Equally important is the role of E2 receptor (ER), as studies indicate that ER populations in several tissue sites may significantly change during stress and aging. Such changes may affect the patient's susceptibility to neurological disorders including stroke and greatly affect the response to selective E2 receptor modulators (SERMs). Replacement therapies may be inefficient with low ER levels. The goal of this review paper is to discuss an animal model that will allow investigations of the potential therapeutic effects of E2 and its derivatives in stroke. We hypothesize that E2 neuroprotection is, in part, receptor mediated. This hypothesis is a proof-of-principle approach to demonstrate a role for specific ER subtypes in E2 neuroprotection. To accomplish this, we use a retroviral-mediated gene transfer strategy that expresses subtypes of the ER gene in regions of the rat brain most susceptible to neuronal damage, namely, the striatum and the cortex. The animal model is exposed to experimental stroke conditions involving middle cerebral artery occlusion (MCAo) method, and eventually the extent of neuronal damage will be evaluated. A reduction in neuronal damage is expected when E2 is administered with specific ER subtypes. From this animal model, an optimal E2 dose and treatment regimen can be determined. The animal model can help identify potential E2-like therapeutics in stroke and screen for beneficial or toxic additives present in commercial E2 preparations that are currently available. Such studies will be informative in designing drug therapies for stroke.

【 授权许可】

CC BY