Abstracts

RATIONALE: Brain N-acetyl-aspartate (NAA) variations in proton magnetic resonance spectroscopy (H-MRS) and changes in the clinical measures gave rise to its acceptance as a putative neuronal marker in various neurodegenerative diseases. To study the role of mitochondrial synthesized NAA in brain energy metabolism during chronic epilepsy we performed in vivo localized H-MRS and in vitro measurement of mitochondrial oxidative phosphorylation in hippocampal and parahippocampal tissue of the pilocarpine model of chronic epilepsy. METHODS: Status epilepticus was induced in 8 male Whistar-rats by systemic injection of pilocarpine. 8 untreated rats were used as controls. After development of spontaneous seizures, single-voxel H-MRS of the hippocampal and parahippocampal regions was performed. Mitochondrial respiratory chain enzyme activities (NADH:CoQ oxidoreductase and cytochrome c oxidase) in the dissected hippocampal subfields were measured spectrophotometrically and oxygen consumption of tissue slices was determined by high resolution respirometry. RESULTS: H-MRS of hippocampus showed in the rats with spontaneous seizures statistically significant decreased NAA signals compared to controls and also to ipsilateral parahippocampal gyrus (NAA:Cr 16.2% versus 18.6%; NAA:Cho 10.6% versus 12.3%) but was normal for lactate, choline and creatine. The in vitro analysis of hippocampus in these rats revealed a specific deficiency of NADH:CoQ oxidoreductase activity (complex I of mitochondrial respiratory chain) and a corresponding altered slice oxygen consumption of the CA3 and CA1 pyramidal subfields. CONCLUSIONS: Our results suggest that NAA levels are closely correlated to mitochondrial energy metabolism and may serve as an indicator of degenerative changes in cell metabolism in epilepsy measured by non-invasive MR techniques.