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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 &lt; 0.001), glutamate/total creatine ( p &lt; 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.

In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination