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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024605-06
Application #
3409339
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Young, R S; During, M J; Donnelly, D F et al. (1993) Effect of anoxia on excitatory amino acids in brain slices of rats and turtles: in vitro microdialysis. Am J Physiol 264:R716-9
Perry, V L; Young, R S; Aquila, W J et al. (1993) Effect of experimental Escherichia coli meningitis on concentrations of excitatory and inhibitory amino acids in the rabbit brain: in vivo microdialysis study. Pediatr Res 34:187-91
Young, R S; Petroff, O A; Aquila, W J et al. (1992) Hyperglycemia and the rate of lactic acid accumulation during cerebral ischemia in developing animals: in vivo proton MRS study. Biol Neonate 61:235-42
Young, R S; During, M J; Aquila, W J et al. (1992) Hypoxia increases extracellular concentrations of excitatory and inhibitory neurotransmitters in subsequently induced seizure: in vivo microdialysis study in the rabbit. Exp Neurol 117:204-9
Young, R S; Petroff, O A; Aquila, W J et al. (1991) Effects of glutamate, quisqualate, and N-methyl-D-aspartate in neonatal brain. Exp Neurol 111:362-8
Young, R S; Petroff, O A; Chen, B et al. (1991) Preferential utilization of lactate in neonatal dog brain: in vivo and in vitro proton NMR study. Biol Neonate 59:46-53
Young, R S; Petroff, O A (1990) Neonatal seizure: magnetic resonance spectroscopic findings. Semin Perinatol 14:238-47
Young, R S; Petroff, O A; Novotny Jr, E J et al. (1990) Neonatal excitotoxic brain injury. Physiologic, metabolic, and pathologic findings. Dev Neurosci 12:210-20
Herness, M S (1989) A dissociation procedure for mammalian taste cells. Neurosci Lett 106:60-4
Young, R S; Chen, B; Petroff, O A et al. (1989) The effect of diazepam on neonatal seizure: in vivo 31P and 1H NMR study. Pediatr Res 25:27-31

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