Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplan...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neural engineering 2017-06, Vol.14 (3), p.036014
Main Authors: Shultz, Robert B, Wang, Zhicheng, Nong, Jia, Zhang, Zhiling, Zhong, Yinghui
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - drug effects
drug delivery
Drug Implants - administration & dosage
Female
hydrogel
Hydrogels - chemistry
Injections, Spinal - methods
myelination
Nerve Fibers, Myelinated - drug effects
Nerve Fibers, Myelinated - pathology
Nerve Regeneration - drug effects
Nerve Regeneration - physiology
oligodendrogenesis
Oligodendroglia - drug effects
Oligodendroglia - pathology
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries - drug therapy
Spinal Cord Injuries - pathology
Spinal Cord Injuries - physiopathology
spinal cord injury
thyroid hormone
Treatment Outcome
Triiodothyronine - administration & dosage
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3′, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.
ISSN:1741-2560
1741-2552
DOI:10.1088/1741-2552/aa6450