Abstract

Myelin is a component of the nervous system that is disrupted in multiple sclerosis, resulting in neuro-axonal degeneration. The longitudinal effect of chronic cuprizone-induced demyelination was investigated in the cerebral gray and white matter of treated mice and the spontaneous remyelination upon treatment interruption. Multimodal Magnetic Resonance Imaging and a Cryoprobe were used at 11.7T to measure signal intensity ratios, T2 values and diffusion metrics. The results showed significant and reversible modifications in white matter and gray matter regions such as in the rostral and caudal corpus callosum, the external capsule, the cerebellar peduncles, the caudate putamen, the thalamus, and the somatosensory cortex of treated mice. T2 and radial diffusivity metrics appeared to be more sensitive than fractional anisotropy, axial diffusivity or mean diffusivity to detect those cuprizone-induced changes. In the gray matter, only signal and T2 metrics and not diffusion metrics were sensitive to detect any changes. Immunohistochemical qualitative assessments in the same regions confirmed demyelination and remyelination processes. These multimodal data will provide better understanding of the dynamics of cuprizone-induced de- and remyelination in white and gray matter structures, and will be the basis to test therapies in experimental models.

Highlights

  • The myelin sheath is an essential component of the vertebrate nervous system enabling an accelerated conduction of nerve impulses together with reduced energy consumption

  • Signal enhancement was clearly visible from the T2w images at 12 weeks of TX in rostral corpus callosum (rCC), caudate putamen (CPu), external capsule (EC), cerebellar peduncles (CP), caudal corpus callosum (cCC), thalamic nuclei (TH), and S1 (Figure 1, middle column) and some recovery was visible at 12 weeks with no TX (Figure 1, right column) compared to the pre-TX baseline signal (Figure 1, left column)

  • We used the chronic CPZ demyelinating model and we showed that ultra-high-field Magnetic Resonance Imaging (MRI) with a CryoProbeTM was sensitive

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Summary

Introduction

The myelin sheath is an essential component of the vertebrate nervous system enabling an accelerated conduction of nerve impulses together with reduced energy consumption. Cuprizone Demyelination and Remyelination of normal conduction and functional recovery, but it may prevent axonal and neuronal degeneration Such a neuroprotective role of myelin could be important in the cortical gray matter (GM) where myelin sheaths, despite being less abundant, could play a crucial role in neuronal survival (Kang et al, 2013). The existence of GM demyelinating cortical lesions in the brains of MS subjects, which are known to be an important hallmark of MS (Kidd et al, 1999; Kutzelnigg et al, 2005; Nelson et al, 2008; Geurts et al, 2011; Mike et al, 2011; Staugaitis et al, 2012), has recently been demonstrated Such cortical demyelination is thought to appear during the first stages of the disease, but subsequently becomes increasingly pronounced during the later phases. Efficient remyelinating abilities have been observed in such lesions, with an even higher efficiency than in white matter (WM) lesions (Chang et al, 2012)

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