Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination

Ryutaro Yano, Junichi Hata, Yoshifumi Abe, Fumiko Seki, Keitaro Yoshida, Yuji Komaki, Hideyuki Okano, Kenji Tanaka

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Diffusion tensor imaging (DTI) is widely used to evaluate microstructural variations in brain tissue. In particular, fractional anisotropy (FA), reflecting the magnitude and orientation of anisotropic water diffusion, allows us to detect pathological events in white matter. An ex vivo DTI study coupled with histological assessment is an efficient strategy to evaluate the myelination process, i.e. demyelination and remyelination. The relationship between DTI values and myelin content or the individual cellular components such as oligodendrocytes, microglia, and astrocytes during both processes of demyelination and remyelination are not well-understood. To address this issue, we employed a cuprizone-inducible demyelination mouse model. Demyelination can be induced in this model during cuprizone exposure and termination of cuprizone exposure induces remyelination. We fed the mice cuprizone-containing chow for 4 weeks and then normal chow for an additional 4 weeks. The ex vivo DTI was performed to evaluate the white matter profiles observed by FA, mean diffusivity (MD), and radial diffusivity (RD) at both demyelinating and remyelinating time points, and then we evaluated histological properties at the same time points. The results indicated a gradual FA decrease during the cuprizone treatment (0, 2, 3, 4 weeks). A lower peak was seen at 1 week after the normal chow was resumed, with recovery to baseline at 2 and 4 weeks. MD and RD showed an opposing pattern to that of FA. These DTI values were positively or negatively correlated with myelin content regardless of the status of the white matter. The RD value was more sensitive to myelination status than FA and MD. We have clarified the temporal changes in the DTI values coupled with histological properties over both the demyelination and remyelination processes.

Original languageEnglish
JournalNeurochemistry International
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Cuprizone
Diffusion Tensor Imaging
Demyelinating Diseases
Anisotropy
Myelin Sheath
Oligodendroglia
Microglia
Astrocytes
Water
Brain

Keywords

  • Astrocyte
  • Immunohistochemistry
  • Microglia
  • MRI
  • Oligodendrocyte
  • Oligodendrocyte precursor cell

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Quantitative temporal changes in DTI values coupled with histological properties in cuprizone-induced demyelination and remyelination. / Yano, Ryutaro; Hata, Junichi; Abe, Yoshifumi; Seki, Fumiko; Yoshida, Keitaro; Komaki, Yuji; Okano, Hideyuki; Tanaka, Kenji.

In: Neurochemistry International, 2017.

Research output: Contribution to journalArticle

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AU - Yoshida, Keitaro

AU - Komaki, Yuji

AU - Okano, Hideyuki

AU - Tanaka, Kenji

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AB - Diffusion tensor imaging (DTI) is widely used to evaluate microstructural variations in brain tissue. In particular, fractional anisotropy (FA), reflecting the magnitude and orientation of anisotropic water diffusion, allows us to detect pathological events in white matter. An ex vivo DTI study coupled with histological assessment is an efficient strategy to evaluate the myelination process, i.e. demyelination and remyelination. The relationship between DTI values and myelin content or the individual cellular components such as oligodendrocytes, microglia, and astrocytes during both processes of demyelination and remyelination are not well-understood. To address this issue, we employed a cuprizone-inducible demyelination mouse model. Demyelination can be induced in this model during cuprizone exposure and termination of cuprizone exposure induces remyelination. We fed the mice cuprizone-containing chow for 4 weeks and then normal chow for an additional 4 weeks. The ex vivo DTI was performed to evaluate the white matter profiles observed by FA, mean diffusivity (MD), and radial diffusivity (RD) at both demyelinating and remyelinating time points, and then we evaluated histological properties at the same time points. The results indicated a gradual FA decrease during the cuprizone treatment (0, 2, 3, 4 weeks). A lower peak was seen at 1 week after the normal chow was resumed, with recovery to baseline at 2 and 4 weeks. MD and RD showed an opposing pattern to that of FA. These DTI values were positively or negatively correlated with myelin content regardless of the status of the white matter. The RD value was more sensitive to myelination status than FA and MD. We have clarified the temporal changes in the DTI values coupled with histological properties over both the demyelination and remyelination processes.

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