In vivo monitoring of rat brain metabolites during vigabatrin treatment using localized 2D-COSY |
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Authors: | Welch John W R Bhakoo Kishore Dixon Ruth M Styles Peter Sibson Nicola R Blamire Andrew M |
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Affiliation: | MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. |
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Abstract: | A two-dimensional COSY-based localization sequence was designed to allow the in vivo monitoring of proton metabolites in rat brain [particularly gamma-aminobutyric acid (GABA), glutamine, taurine and myo-inositol]. The sequence incorporated OSIRIS signal localization, B1-insensitive water suppression and phase-sensitive COSY acquisition. The method was used to study the effects of the GABA-transaminase inhibitor vigabatrin on rat brain metabolite concentrations. Wistar rats were treated daily for 3 days with an oral dose of vigabatrin (200 mg/kg, n = 4). Localized COSY spectra were obtained during a 120 min acquisition from a 270 microl central brain voxel and compared with nine untreated control animals. Significant elevations were observed in GABA (267% of control, p < 0.005, Mann-Witney test), glutamine (130% of control, p < 0.005) and taurine (113% of control, p < 0.05). Changes in GABA and taurine were consistent with previous data on the action of Vigabatrin, and support a previously hypothesized link between these compounds. The increase in glutamine was more surprising and may reflect the balance between the level and/or site of GABA-transaminase inhibition and downregulation of GABA synthesis. |
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Keywords: | two‐dimensional NMR ISIS COSY vigabatrin GABA |
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