The Ventral Medulla and the Sudden Infant Death Syndrome (PI, Project 1: Protective Responses and Brainstem Analysis in the Sudden Infant Death Syndrome)

This project is a component of a program project directed by Dr. Kinney. This program was just funded for the third (five-year) cycle, receiving a score of 1.1 (0.2%). Despite an almost 50% decline in the incidence of the sudden infant death syndrome (SIDS) following the 1992 national recommendation for the supine sleep position, SIDS remains a leading cause of postneonatal infant mortality in the United States. Our hypothesis is that a neurological subset of SIDS cases is due to developmental abnormalities in the medullary 5-HT system that interfere with protective homeostatic responses to potentially life-threatening, but often occurring, events during infant sleep, such as hypoxia, hypercarbia, asphyxia, thermal stresses, blood pressure changes, and/or reflex apnea. "Medullary 5-HT system" refers to an inter-related group of 5-HT and non-5-HT neurons in the raphe and extra-raphe reticular formation and the ventral surface of the medulla that influence homeostatic functions, i.e., respiration, chemosensitivity to carbon dioxide and oxygen, upper airway reflexes, blood pressure control, heart rate, thermoregulation, and sleep. The overall goal is to define in-depth the organization, function, and development of the medullary 5-HT system, the mechanism(s) by which its dysfunction results in sudden death, and potential causes of this dysfunction. In Project 1 we are analyzing the neurochemical organization of the medullary 5-HT system in early human life and are further characterizing its pathology in SIDS cases. We are expanding upon the observations of the previous cycles and examining the relationship of the medullary 5-HT system in regards to its relationship to the GABAergic and substance P systems, sex steroid hormones, and responses to chronic intermittent hypoxia. The areas of relevance to the mission of the NICHD Developmental Disabilities Centers are: 1 and 2.