The over-arching aim of Core B is to provide to each Project, access to tissue and results relevant to the functional status of ovariectomized rats maintained in two experiments conducted in a standardized setting. In phases I and 11, five treatment regimens [vehicle, estrogen, diarylpropionitrile (DPN), progesterone, or estrogen + progesterone], implemented after 3 different post-ovariectomy delays, will be evaluated for their ability to reverse the functional deficits associated with OVX in young adult (4-month old) and after one delay in reproductive senescent (10 month old) rats. In a subsequent experiment (phase 111), the neuroprotective efficacy of the same treatment regimens will be assessed in the transient middle cerebral artery occlusion (tMCAO) model of stroke. The assessment of functional outcomes at the different post-ovariectomy delays will provide the critical data that allows the individual projects to relate changes in the functions of estrogen receptors, progesterone receptors and intracellular calcium channels, to specific periods of sensitivity or refractoriness to hormone receptor-targeted interventions. Core B will provide standardized implementation of the experimental variables;outcome assessments, environment, and animal husbandry needed for the project experiments, and provide for highly efficient leveraging of resources used by all projects, including staff and animals. To this end. Core B will procure, identify and monitor rats used in the experiments, perform all surgical interventions (ovariectomy, implantation of Silastic pellets and tMCAO), and perform comprehensive analyses of the functional status of the rats in the context of the different treatment regimens. Core B will in addition provide non-behaviorally characterized rats that will have been ovariectomized and exposed to the 5 treatment to Project 2 for synaptoneurosomal fraction preparation, and will maintain availability of neonatal brain tissue for the generation of primary neuronal cultures.
The ovariectomized rat is an experimental model that will allow the investigators to study how hormones support healthy brain function, ultimately leading to the design of effective hormone based therapy for treating brain dysfunction in humans. The transient middle cerebral artery occlusion (tMCAO) model simulates conditions of a stroke-related injury, and is also used to predict the efficacy of hormone therapy.
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