Cortical Demyelination Is Prominent in the Murine Cuprizone Model and Is Strain-Dependent

Abstract

The cuprizone model of toxic demyelination in the central nervous system is commonly used to investigate the pathobiology of remyelination in the corpus callosum. However, in human demyelinating diseases such as multiple sclerosis, recent evidence indicates a considerable amount of cortical demyelination in addition to white matter damage. Therefore, we have investigated cortical demyelination in the murine cuprizone model. To induce demyelination, C57BL/6 mice were challenged with 0.2% cuprizone feeding for 6 weeks followed by a recovery phase of 6 weeks with a cuprizone-free diet. In addition to the expected demyelination in the corpus callosum, the cortex of C57BL/6 mice was completely demyelinated after 6 weeks of cuprizone feeding. After withdrawal of cuprizone the cortex showed complete remyelination similar to that in the corpus callosum. When C57BL/6 mice were fed cuprizone for a prolonged period of 12 weeks, cortical remyelination was significantly delayed. Because interstrain differences have been described, we also investigated the effects of cuprizone on cortical demyelination in BALB/cJ mice. In these mice, cortical demyelination was only partial. Moreover, cortical microglia accumulation was markedly increased in BALB/cJ mice, whereas microglia were absent in the cortex of C57BL/6 mice. In summary, our results show that cuprizone feeding is an excellent model in which to study cortical demyelination and remyelination, including contributing genetic factors represented by strain differences. (Am J Pathol

Stereological Evidence for De/Re-Generation of Myelin Sheaths in Aged Brain White Matter of Female Rats

“…In previous studies on aged monkey brains, two of the age-related alterations seen in this study in myelin sheaths (local splitting of the major dense lines and the formation of myelin balloons) were observed in the anterior commissure, primary visual cortex and corpus callosum (Peters et al, 2000;Peters and Sethares, 2002;Sandell and Peters, 2003). Moreover, it has been reported that myelin sheath changes were also involved in various diseases (Lassmann et al, 1997;Myers, 1998;Biffiger et al, 2000), and in various experimental conditions (Blakemore, 1978;Chang, 1990;Anderson et al, 1998;Franco-Pons et al, 2007;Karim et al, 2007;Skripuletz et al, 2008;). Similar age-related changes in the myelin sheaths of elderly rats were observed in this study (Fig.4A, Fig.4B).…”

Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination

“…A number of reports have indicated that this demyelination model also displays abnormal behaviors and cognitive defects that are believed to be a direct result of demyelination [28,29,37,38] . The behavior changes may reflect neuronal abnormalities, like anxiety and cognitive impairment, and mimic, at least partially, schizophrenia symptoms in humans.…”

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

“…39 Following the confirmation of the efficacy of this model of toxic demyelination in the CNS, the polyplex formulations were injected followed by imaging the animal at 0, 15, 30, 60, 120, 180 min, and 24 h post injection. Figure 7 shows the distribution of the fluorescently labeled plasmid encoding CD200 from the injection site to the various tissues and organs including the lymph nodes, liver, brain, and finally kidneys.…”

“…The demyelination was confirmed by Luxol Fast Blue staining according to Kluver-Barrera procedure as described elsewhere. 39 To track nanoparticles in the body of the mice, fluorescently labeled plasmid encoding CD200 by GelRed was used, and the polyplexes at the highest C/P ratio of 8 were prepared as described earlier (vide supra). Mice were injected via the tail vein at a final volume of 100 μL of the polyplex formulation.…”