This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of
cuprizone-induced
demyelination as detected using in vivo 7 T
proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or
cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using
a 7 T magnetic resonance imaging scanner. All
proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the
cuprizone-induced rats had significantly higher concentrations of
glutamate (p = 0.001),
gamma-aminobutyric acid (p = 0.019), and
glutamate +
glutamine (p = 0.001); however,
creatine +
phosphocreatine (p = 0.006) and myo-
inositol (p = 0.001) concentrations were lower. In addition, we found that the
glutamine and
glutamate complex/total
creatine (p < 0.001),
glutamate/total
creatine (p < 0.001), and
GABA/total
creatine (p = 0.002) ratios were significantly higher in
cuprizone-treated rats than in control rats. Our results showed that
cuprizone-induced neuronal
demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation,
mitochondrial dysfunction, and astrocytic
necrosis.