title: Remyelination after spinal cord injury: is it a target for repair?
abstract: After spinal cord injury (SCI) there is prolonged and dispersed oligodendrocyte cell death that is responsible for widespread demyelination. To regenerate this lost myelin, many investigators have transplanted myelin-producing cells as a treatment for contusive SCI. There are several documented examples of cellular transplantation improving function after injury, with the degree of myelin regeneration correlating with functional recovery. On the basis of these findings, remyelination is hypothesized to be a beneficial strategy to promote recovery after injury. As cellular transplantation is now entering clinical trials for treatment of SCI, it is important to dissect carefully whether accelerating remyelination after SCI is a valid clinical target. In this review we will discuss the consequences of demyelination and the potential benefits of remyelination as it relates to injury. Prolonged demyelination is hypothesized to enhance axonal vulnerability to degeneration, and is thereby thought to contribute to the axonal degeneration that underlies the permanent functional losses associated with SCI. Currently, strategies to promote remyelination after SCI are largely limited to cellular transplantation. This review discusses those strategies as well as new, and largely untested, modes of therapy that aim to coax endogenous cells residing adjacent to the injury site to differentiate in order to replace lost myelin.
authors.affiliation: ICORD, University of British Columbia, Vancouver, British Columbia, Canada; (International Collaboration on Repair Discoveries), Neuroscience Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2 N 4N1, Canada; The Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. Electronic address: jrplemel@ucalgary.ca.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Plemel
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2 N 4N1, Canada; The Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. Electronic address: mbkeough@ucalgary.ca.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Keough
authors.affiliation: ICORD, University of British Columbia, Vancouver, British Columbia, Canada; Zoology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: Duncan@icord.org.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Duncan
authors.affiliation: ICORD, University of British Columbia, Vancouver, British Columbia, Canada; (International Collaboration on Repair Discoveries), Neuroscience Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Sparling
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2 N 4N1, Canada; The Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; The Department of Oncology, University of Calgary, Calgary, Alberta, Canada. Electronic address: vyong@ucalgary.ca.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2 N 4N1, Canada; The Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. Electronic address: pstys@ucalgary.ca.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Stys
authors.affiliation: ICORD, University of British Columbia, Vancouver, British Columbia, Canada; (International Collaboration on Repair Discoveries), Neuroscience Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada; Zoology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: tetzlaff@icord.org.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
mesh_terms: D000818:Animals; D006801:Humans; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology*
keywords: Axon degeneration; Myelin; Oligodendrocyte; Oligodendrocyte precursor cell; Remyelination; Spinal cord injury