Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model

Abstract

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.