title: Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Shultz
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Nong
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004343:Drug Implants / Q000008:administration & dosage*; D005260:Female; D020100:Hydrogels / Q000737:chemistry; D007278:Injections, Spinal / Q000379:methods*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000008:administration & dosage*
chemical_list: D004343:Drug Implants; D020100:Hydrogels; D014284:Triiodothyronine