Plant polyprenols reduce demyelination and recover impaired oligodendrogenesis and neurogenesis in the cuprizone murine model of multiple sclerosis.

Recent studies showed hepatoprotective, neuroprotective, and immunomodulatory properties of polyprenols isolated from the green verdure of Picea abies (L.) Karst. This study aimed to investigate effects of polyprenols on oligodendrogenesis, neurogenesis, and myelin content in the cuprizone demyelination model. Demyelination was induced by 0.5% cuprizone in CD-1 mice during 10 weeks. Nine cuprizone-treated animals received daily injections of polyprenols intraperitoneally at a dose of 12-mg/kg body weight during Weeks 6-10. Nine control animals and other nine cuprizone-treated received sham oil injections. At Week 10, brain sections were stained for myelin basic protein, neuro-glial antigen-2, and doublecortin to evaluate demyelination, oligodendrogenesis, and neurogenesis. Cuprizone administration caused a decrease in myelin basic protein in the corpus callosum, cortex, hippocampus, and the caudate putamen compared with the controls. Oligodendrogenesis was increased, and neurogenesis in the subventricular zone and the dentate gyrus of the hippocampus was decreased in the cuprizone-treated group compared with the controls. Mice treated with cuprizone and polyprenols did not show significant demyelination and differences in oligodendrogenesis and neurogenesis as compared with the controls. Our results suggest that polyprenols can halt demyelination, restore impaired neurogenesis, and mitigate reactive overproduction of oligodendrocytes caused by cuprizone neurotoxicity.

Quantitative assessment of demyelination in ischemic stroke in vivo using macromolecular proton fraction mapping.

A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used to quantify demyelination in the transient middle cerebral artery occlusion (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2, proton density, and apparent diffusion coefficient) were compared with histological and immunohistochemical markers of demyelination (Luxol Fast Blue stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky stain), and inflammation (Iba1 immunofluorescence) in three animal groups ( n = 5 per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density (OD) were significantly reduced in the ischemic lesion on all days after MCAO relative to the symmetrical regions of the contralateral hemisphere. Percentage changes in MPF and LFB OD in the ischemic lesion relative to the contralateral hemisphere significantly differed on the first day only. Percentage changes in LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not correlate with other MRI parameters. MPF also did not correlate with other histological variables. Addition of T2 into multivariate regression further improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction of the edema effect. This study provides histological validation of MPF as an imaging biomarker of demyelination in ischemic stroke.