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Neuroscience. 2013 Dec 19;254:1-17. doi: 10.1016/j.neuroscience.2013.09.011. Epub 2013 Sep 14.

Compression injury in the mouse spinal cord elicits a specific proliferative response and distinct cell fate acquisition along rostro-caudal and dorso-ventral axes.

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  • 1Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, 4400 V Street, Sacramento, CA 95817, USA; Institute of Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, 2425 Stockton Boulevard, Sacramento, CA 95817, USA.

Abstract

Harnessing the regenerative capabilities of endogenous precursor cells in the spinal cord may be a useful tool for clinical treatments aimed at replacing cells lost as a consequence of disease or trauma. To better understand the proliferative properties and differentiation potential of the adult spinal cord after injury, we used a mouse model of compression spinal cord injury (SCI). After injury, adult mice were administered BrdU to label mitotic cells and sacrificed at different time-points for immunohistochemical analysis. Our data show that the rate of proliferation increased in all regions of the spinal cord 1day after injury, peaked after 3days, and remained elevated for at least 14days after injury. Proliferation was greater at the injury epicenter than in rostral and caudal adjacent spinal segments. The number of proliferative cells and rate of proliferation varied between dorsal and ventral regions of the spinal cord and between the gray and white matter. Newly generated cells expressed markers for progenitor cells (Nestin and Olig2), oligodendrocytes (Sox10), astrocytes (S100b and glial fibrillary acidic protein), and microglia (Iba1), but not neuronal markers (Map2 and NeuN). Marker expression varied with regard to the dorso-ventral region, rostro-caudal proximity to the injury epicenter, and time after injury. At early time-points after injury, BrdU(+) cells mainly expressed microglial/macrophage and astrocytic markers, while at these same time-points in the control spinal cord the mitotic cells predominately expressed oligodendrocyte and oligodendrocyte progenitor cell markers. The profile of proliferation and cell fate marker expression indicates that after moderate compression, the spinal cord has the capacity to generate a variety of glial cells but not neurons, and that this pattern is space and time specific. Future studies should focus on ways to control proliferation and cell fate after injury to aid the development of cell replacement treatments for SCI.

Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

BMS; Basso Mouse Scale; CC; DGM; DWM; GFAP; PBS; PFA; SCI; VGM; VWM; cell fate; central canal; dorsal gray matter; dorsal white matter; glial fibrillary acidic protein; paraformaldehyde; phosphate buffered saline; precursor cells; proliferation; spinal cord injury; ventral gray matter; ventral white matter

PMID:
24042034
[PubMed - in process]
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