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

A. McDonough, A. N. Hoang, A. M. Monterrubio, S. Greenhalgh, Veronica Martinez-Cerdeno

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalNeuroscience
Volume254
DOIs
StatePublished - Dec 19 2013

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Spinal Cord
Wounds and Injuries
Oligodendroglia
Spinal Cord Injuries
Cell Proliferation
Bromodeoxyuridine
Stem Cells
Nestin
Spinal Cord Compression
Glial Fibrillary Acidic Protein
Microglia
Neuroglia
Astrocytes
Macrophages
Neurons

Keywords

  • Cell fate
  • Precursor cells
  • Proliferation
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Compression injury in the mouse spinal cord elicits a specific proliferative response and distinct cell fate acquisition along rostro-caudal and dorso-ventral axes. / McDonough, A.; Hoang, A. N.; Monterrubio, A. M.; Greenhalgh, S.; Martinez-Cerdeno, Veronica.

In: Neuroscience, Vol. 254, 19.12.2013, p. 1-17.

Research output: Contribution to journalArticle

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