Animal and Behavior Core

项目总结

PROJECT SUMMARY Perinatal brain injury induced by hypoxia ischemia remains a leading cause of intellectual and physical disability throughout the world. The use of rodent models will contribute to both prevention and treatment of life-long impairment in infants. The Animal and Behavior Core (Core B) will provide rats subjected to hypoxia ischemia (H/I) with and without prior inflammation for four integrated Projects. To maintain consistency across experiments, Core B will also treat pups with the proposed neuroprotective treatments, including hypothermia. To facilitate data interpretation, the Animals and Behavior Core will also provide standard ratings of crude histopathology to facilitate determination of efficacy of neuroprotective interventions. The variability of injury is well recognized, and such rankings are often used to determine neuroprotection effects in mildly injured rats separately from severely injured rats. This will particularly inform experiments that require tissue to be homogenized, such as western blotting, lipid raft isolation and NMR, and therefore do not include histological information. These a priori rankings will be used to track both the consistency of the injury over time, and also give us a broader picture of potential efficacy of neuroprotective compounds. Core B will organize and maintain banked samples from Projects I-IV, and make them available to the laboratories of Projects I-IV. Such Core activities are designed to circumvent the need to produce new animals for pilot experiments that may arise as data collection progresses. The Animals and Behavior Core will execute novel combinations of behavioral assays to determine the extent of dysregulation within the cerebellum and reciprocal connections between the cerebellum and other brain regions. Finally, data collection and communication concerning progress of experiments will be facilitated by implementation of an IntraNet accessible relational database. This database will be maintained by Core B personnel. This Core will also collect tissue at the appropriate time post H/I for specific experiments and track use of tissue samples in the intrarelational database. The overall goal of the Animal and Behavior Core is to assure quality control and cross-project integration to maximize the potential for detecting molecular and behavioral impairments caused by H/I and/or perinatal systemic inflammation, and the effects of therapeutic interventions. A critical strength of this Program Project Grant is the use of the same procedures to generate hypoxia ischemia and treatments. This will enable Projects I-IV to make conclusions quickly and revise experimental approaches if necessary based on data collected from other Projects.