(Core C) The overall objective of the core is to facilitate efficient preparation, distribution and analysis of ferret brain tissue among Projects 1-3 for studies of normal development and development following early hypoxic brain injury. The Ferret model has distinct advantages over existing rodent models for studies central to this program project focused on novel late migratory streams (Project 1), oligodendrocyte precursor cell development (Project 2) and hypoxia/HIF pathway signaling (Project 3). These advantages include: (1) a gyrencephalic brain with a protracted period of postnatal brain development and (2) the existence of a distinct outer subventricular zone and late migrating neuronal streams similar to human MMS and DMS. Core C will promote synergy and interaction among the three projects by facilitating integrated Ferret tissue utilization. We propose the following two specific objectives: Objective 1: Optimal preparation and utilization of brain tissue from a unique small animal, gyrencephalic model of normal cortical development in the ferret (Mustela putorius) Objective 2: Further develop a small animal model of human preterm white matter injury in the gyrencephalic ferret suitable for translational studies of pathogenesis and therapy. Unlike rodents, Ferrets are an FDA regulated species. The core will be responsible for developing and maintaining appropriate protocols for the compassionate care and use of Ferrets. All protocols will be developed in consultation with University of California, San Francisco Laboratory Animal Resource Center (LARC) veterinarians. The Core will maintain annual regulatory approval through the UCSF Institutional Animal Care and Use Committee (IUCUC). The Core will carry out all animal surgeries and postsurgical care along with LARC veterinarians. A major function of the core will be to organize efficient use of animal tissue by optimizing sharing of tissue among compatible projects. The Program Project Administrative Committee will determine allocation and prioritization of animals and tissue. The core will be responsible for developing and testing reagents and techniques for tissue analysis. Finally the core will develop conditions for the chronic hypoxia translational model of newborn brain injury. This will include Ferret brain MR imaging, an application with potential for increasing translational relevance by comparison with complementary human data.

National Institute of Health (NIH)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of California San Francisco
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Yuen, Tracy J; Silbereis, John C; Griveau, Amelie et al. (2014) Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell 158:383-96