This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A.
SPECIFIC AIMS The specific aims of this proposal are intended to reduce the prevalence of white matter damage in preterm infants. Biomarkers now measurable in minute quantities of serum, and thus suitable for studies of the smallest and most vulnerable humans, can tell us much about the exposures that lead to neonatal brain damage. Based on human, animal and in vitro studies, the sequence of events leading to white matter damage appears to originate with initiators (e.g., microbial organisms) of maternal, fetal and neonatal inflammatory responses. These responses are characterized by the synthesis of damage promoters (e.g., inflammatory cytokines), and can be limited by inflammation modulators (e.g., cytokine receptor antagonists, cytokine-binding proteins, and anti-inflammatory cytokines). In addition, protectors (e.g., hormones and growth promoters) can help prevent the deleterious effects of damage promoters on oligodendrocytes, the cells that characterize white matter in the brain. The following are the specific aims of the proposal: 1. To identify the antecedents of ultrasound-defined cerebral white matter damage in a sample of 1,800 infants born between 23.0 and 27.9 weeks of gestation. 2. To identify initiators and damage promoters that increase the risk of ultrasound-defined cerebral white matter damage so that clinical trials can be designed to evaluate how effectively a reduction or blockade of initiators or damage promoters prevents white matter damage. 3. To identify inflammation modulators and protectors that reduce the risk of ultrasound-defined cerebral white matter damage so that clinical trials can be designed to evaluate the effectiveness of these modulators and protectors to prevent white matter damage. 4. To maintain contact with the parents of each surviving child in order to maximize participation in later follow-up studies, thereby creating the opportunity to evaluate how initiators of damage promotion, damage prom
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