Format

Send to

Choose Destination
Exp Neurol. 2016 Sep;283(Pt A):330-40. doi: 10.1016/j.expneurol.2016.06.033. Epub 2016 Jul 3.

A mouse model for testing remyelinating therapies.

Author information

1
Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States. Electronic address: bbai@renovoneural.com.
2
Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
3
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.
4
Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States; Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.

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.

KEYWORDS:

Differential remyelination; Internodal length; Mice; Myelin; Therapeutic; Ultrastructure

PMID:
27384502
PMCID:
PMC5207347
DOI:
10.1016/j.expneurol.2016.06.033
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center