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Fate of endogenous neural stem/progenitor cells following spinal cord injury in the adult mammal

Posted on:2004-03-07Degree:Ph.DType:Dissertation
University:University of California, San DiegoCandidate:Horky, Laura LFull Text:PDF
GTID:1464390011973519Subject:Biology
Abstract/Summary:
The adult mammalian spinal cord contains neural stem/progenitor cells that slowly multiply throughout life and differentiate exclusively into glia. We do not know the fate of these cells after spinal cord injury. Recent studies have described a phenomenon of massive cell proliferation within 24 hours after spinal cord injury. Whether these proliferating cells are stem/progenitor cells is not known with certainty. Using the mitotic indicator bromodeoxyuridine (BrdU), we found that in the adult female Fisher 344 rat, endogenously dividing neural progenitors are acutely vulnerable in response to T8 dorsal hemisection spinal cord injury. We then studied the population of dividing cells in the injury epicenter by delivering BrdU 24 hours after spinal cord injury. Animals were euthanized at five time points ranging from 6 hours to 9 weeks after BrdU delivery. At all time points, we observed evidence of massive cellular proliferation and found dividing cells in the ependyma that immunohistochemically resemble stem/progenitor cells. The major phenotypes of BrdU+ cells in the parenchyma were NG2+ oligodendrocyte progenitors that matured into oligodendrocytes, and a transient population of microglia. Our results suggest that stem/progenitor cells in the uninjured spinal cord are vulnerable to injury but another population of cells rapidly divides after injury and appears to persist in the ependyma and parenchyma. Using a GFP+ chimeric mouse, we also determined that 90% of the dividing cells appear to originate from the spinal cord, whereas 10% originate from the bone marrow. These BrdU+ bone marrow-derived cells do not appear to develop into neural cells.
Keywords/Search Tags:Spinal cord, Stem/progenitor cells
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