In vivo monitoring of rat brain metabolites during vigabatrin treatment using localized 2D-COSY.

Journal article

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.

Authors: Welch, J; Bhakoo, K; Dixon, R; Styles, P; Sibson, N

• Publication status: Published
• Journal: NMR in biomedicine
• Volume: 16
• Issue: 1
• Pages: 47-54
• Publication date: 2003-02-01
• DOI: 10.1002/nbm.809
• EISSN: 1099-1492
• ISSN: 0952-3480
• Language: English
• Keywords: gamma-Aminobutyric Acid; Sensitivity and Specificity; Animals; Rats, Wistar; Rats; Taurine; Magnetic Resonance Spectroscopy; Vigabatrin; Male; Glutamine; Reference Values; Brain; Reproducibility of Results