HEALTH RELATEDNESS: Seizure is the most common neurological complication in the neonatal period and is frequently associated with mental retardation, cerebral palsy, and epilepsy. The long- term objective of this proposal is to elucidate the mechanism of brain injury caused by neonatal seizure, thereby reducing morbidity and mortality due to neonatal seizure.
SPECIFIC AIMS : The experiments in this proposal will: 1. Determine whether charges in inhibitory and excitatory neurotransmitters during neonatal seizure correlate with brain injury. 2. Measure the deterioration in brain energy state during neonatal seizure and assess the relationship between brain energy state and brain injury. 3. Identify the substrates which are critical for energy production during neonatal seizure. 4. Investigate how anticonvulsants affect levels of inhibitory or excitatory neurotransmitters during neonatal seizure and whether anticonvulsants ameliorate changes in brain energy state during- neonatal seizure. 5. Determine whether neuropathologic changes result from or are worsened by systemic complications during seizure. METHODS: To accomplish these aims, sophisticated methodologies will be utilized: 1. Brain energy state during neonatal seizure will be determined in vivo with high resolution 31p NMR spectroscopy. Brain metabolite changes will be assessed with 1H and 13C NMR spectroscopy in vitro. 2. Metabolic flux of substrates utilized during seizure (glucose, lactate, alanine) will be investigated with 13C NMR fractional labelling studies. 3. Neurotransmitter alterations (GABA, glycine, taurine, glutamate) will be determined by in vivo high resolution 1H NMR spectroscopy and by in vitro measurement of neurotransmitter receptor binding. 4. Brain physiologic changes will be measured with EEG and regional cerebral blood flow (14C iodoantipyrine technique). 5. Morphologic alterations will be determined by both light and electron microscopic analysis.
Showing the most recent 10 out of 14 publications
