HEALTH RELATEDNESS: Seizures are the most frequent neurological problem in the neonatal period. These seizures, if prolonged, may be associated with subsequent mental retardation, epilepsy, and cerebral palsy.
SPECIFIC AIMS : 1. To describe the morphologic changes which occur during prolonged seizures in the neonatal dog. 2. To determine the physiologic changes which accompany prolonged seizures and correlate them to the morphologic changes. 3. To assess energy availability and energy utilization during prolonged seizures. 4. To evaluate how energy availability during seizures is affected by substrate limitation (e.g. hypoxemia, hypoglycemia). 5. To determine how physiologic and metabolic changes accompanying prolonged neonatal seizures are affected by anticonvulsant drugs. METHODOLOGY: 1. Morphologic alterations will be determined with light and electron microscopic studies, and with Golgi studies of dendritic development. 2. Cerebral physiologic changes will be measured with electroencephalography and regional cerebral blood flow determinations (14C iodoantipyrine). 3. Energy availability will be evaluated with in vivo measurement of brain high energy phosphate metabolism utilizing 31P Nuclear Magnetic Resonance. Enzymatic assays of frozen brain samples will also be made. 4. Studies to determine the effect of substrate limitation will be carried out by making the animal hypoxemic, hypoglycemic, or hypotensive. 5. The modifying effects of anticonvulsants will be studied by administering phenobarbital, phenytoin, and diazepam. LONG TERM OBJECTIVES: This research proposal will utilize new methodology (31P NMR) which permits non-invasive and non-destructive in vivo measurements of energy availability during neonatal seizures. These experiments are designed to substantially extend our understanding of the pathophysiology of neonatal seizures and thereby lead to more rational treatment.
Showing the most recent 10 out of 14 publications
