A Mouse Model for Testing Remyelinating Therapies

Overview

Journal Exp Neurol

Specialty Neurology

Date 2016 Jul 8

PMID 27384502

Citations 30

Authors

C Brian Bai

Sunny Sun

Andrew Roholt

Emily Benson

Dale Edberg

Satish Medicetty

Ranjan Dutta

Grahame Kidd

Wendy B Macklin

Bruce Trapp

Affiliations

Soon will be listed here.

Abstract

Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and cerebral cortex. Spontaneous remyelination occurred significantly faster in the cerebral cortex than in white matter and reactive astrocytes were more abundant in white matter lesions. Remyelination of white matter and cerebral cortex was therapeutically enhanced by daily injections of thyroid hormone triiodothyronine (T3). In summary, we describe an in vivo demyelination/remyelination paradigm that can be powered to determine efficacy of therapies that enhance white matter and cortical remyelination.

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