Diffusion tensor imaging identifies aspects of therapeutic estrogen receptor β ligand-induced remyelination in a mouse model of multiple sclerosis.

Diffusion tensor imaging identifies aspects of therapeutic estrogen receptor β ligand-induced remyelination in a mouse model of multiple sclerosis.

Publication date: Jun 18, 2019

Diffusion tensor imaging (DTI) has been shown to detect white matter degeneration in multiple sclerosis (MS), a neurodegenerative autoimmune disease that presents with diffuse demyelination of the central nervous system. However, the utility of DTI in evaluating therapeutic remyelination has not yet been well-established. Here, we assessed the ability of DTI to distinguish between remyelination and neuroprotection following estrogen receptor β ligand (Indazole chloride, IndCl) treatment, which has been previously shown to stimulate functional remyelination, in the cuprizone (CPZ) diet mouse model of MS. Adult C57BL/6 J male and female mice received a normal diet (control), demyelination-inducing CPZ diet (9wkDM), or CPZ diet followed by two weeks of a normal diet (i.e., remyelination period) with either IndCl (RM + IndCl) or vehicle (RM + Veh) injections. We evaluated tissue microstructure of the corpus callosum utilizing in vivo and ex vivo DTI and immunohistochemistry (IHC) for validation. Compared to control mice, the 9wkDM group showed decreased fractional anisotropy (FA), increased radial diffusivity (RD), and no changes in axial diffusivity (AD) both in vivo and ex vivo. Meanwhile, RM + IndCl groups showed increased FA and decreased RD ex vivo compared to the RM + Veh group, in accordance with the evidence of remyelination by IHC. In conclusion, the DTI technology used in the present study can identify some changes in myelination and is a valuable translational tool for evaluating MS pathophysiology and therapeutic efficacy.

Concepts Keywords
Autoimmune Diffusion tensor imaging
Central Nervous System Organ systems
Chloride Hormones
Corpus Callosum Branches of biology
Demyelination Neurology
Diffusion Tensor Imaging Magnetic resonance imaging
DTI Neuroimaging
Estrogen Receptor Remyelination
Immunohistochemistry Diffusion MRI
Indazole DTI
Ligand Demyelinating disease
Mice Neuroprotection
Microstructure
Multiple Sclerosis
Myelination
Neurodegenerative
Neuroprotection
Pathophysiology
Vivo
White Matter

Semantics

Type Source Name
gene UNIPROT CPZ
drug DRUGBANK Chlorpromazine
disease MESH demyelination
disease DOID autoimmune disease
disease MESH autoimmune disease
disease DOID multiple sclerosis
disease MESH multiple sclerosis
disease MESH estrogen

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