In vivo monitoring of rat brain metabolites during vigabatrin treatment using localized 2D-COSY.
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.
Welch
John W R
JW
MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Bhakoo
Kishore
K
Dixon
Ruth M
RM
Styles
Peter
P
Sibson
Nicola R
NR
Blamire
Andrew M
AM
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005973:Glutamine / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013654:Taurine / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D020888:Vigabatrin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
D005973:Glutamine; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin