title: Chronic oligodendrogenesis and remyelination after spinal cord injury in mice and rats.
abstract: Adult progenitor cells proliferate in the acutely injured spinal cord and their progeny differentiate into new oligodendrocytes (OLs) that remyelinate spared axons. Whether this endogenous repair continues beyond the first week postinjury (wpi), however, is unknown. Identifying the duration of this response is essential for guiding therapies targeting improved recovery from spinal cord injury (SCI) by enhancing OL survival and/or remyelination. Here, we used two PDGFRα-reporter mouse lines and rats injected with a GFP-retrovirus to assess progenitor fate through 80 d after injury. Surprisingly, new OLs were generated as late as 3 months after injury and their processes ensheathed axons near and distal to the lesion, colocalized with MBP, and abutted Caspr+ profiles, suggesting newly formed myelin. Semithin sections confirmed stereotypical thin OL remyelination and few bare axons at 10 wpi, indicating that demyelination is relatively rare. Astrocytes in chronic tissue expressed the pro-OL differentiation and survival factors CNTF and FGF-2. In addition, pSTAT3+ NG2 cells were present through at least 5 wpi, revealing active signaling of the Jak/STAT pathway in these cells. The progenitor cell fate genes Sox11, Hes5, Id2, Id4, BMP2, and BMP4 were dynamically regulated for at least 4 wpi. Collectively, these data verify that the chronically injured spinal cord is highly dynamic. Endogenous repair, including oligodendrogenesis and remyelination, continues for several months after SCI, potentially in response to growth factors and/or transcription factor changes. Identifying and understanding spontaneous repair processes such as these is important so that beneficial plasticity is not inadvertently interrupted and effort is not exerted to needlessly duplicate ongoing spontaneous repair.
authors.affiliation: Neuroscience Graduate Studies Program.
authors.forename: Zoe C
authors.initials: ZC
authors.lastname: Hesp
authors.forename: Evan Z
authors.initials: EZ
authors.lastname: Goldstein
authors.affiliation: Neuroscience Graduate Studies Program.
authors.forename: Evan A
authors.initials: EA
authors.lastname: Goldstein
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio 43205.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Miranda
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kaspar
authors.affiliation: Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio 43210, and Nationwide Children's Hospital, Columbus, Ohio 43205.
authors.forename: Brain K
authors.identifier: http://orcid.org/0000-0003-2394-0196
authors.initials: BK
authors.lastname: Kaspar
authors.affiliation: Department of Neuroscience, and Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio 43210, and dana.mctigue@osumc.edu.
authors.forename: Dana M
authors.initials: DM
authors.lastname: McTigue
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
keywords: NG2 cell; demyelination; glial scar; growth factor; stem cell; transplant