The CORE section of our application is composed of three components: Administration, Education and Model Development. The Administrative component will be led by Dr. Ment and will include Program, Internal Advisory and External Review Committees. The Center Core is Model Development and Validation. Although there are many models currently in use neonatal cerebral insult, non of them appears to be entirely adequate to describe the conditions following IVH. Our clinical studies have indicated no gross changes observable by sophisticated neuroimaging techniques and thus models that result in unilateral or bilateral destructive lesions are not appropriate for our needs. Our goal in developing and implementing models of both hypoxia and ischemia in neonatal rats will be to adjust the severity of insult so as to not produce large infarcts or wide spread loss of cortical neurons. We hypothesize that much of the damage done by the events that lead to IVH and result from its occurrence may not be caused by widespread neuronal death but by sublethal disturbances of the normal sequence of cerebral development. Some of these disturbances may include alterations in cerebral metabolism, abnormal expression of membrane channels and abnormal intracortical connectivity and synaptogenesis.
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