title: ESTROGEN REPLACEMENT THERAPY FOR STROKE.
abstract: 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 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 express subtypes of the ER gene in regions of the rat brain most susceptible to neuronal damage, namely the striatum and 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.
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Mibel
authors.initials: M
authors.lastname: Pabon
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Tamboli
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Sarosh
authors.initials: S
authors.lastname: Tamboli
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Acosta
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Ike
authors.initials: I
authors.lastname: De La Pena
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL USA.
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan