Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic

Lu Li, Kate M. Harms, P. Britten Ventura, Diane C. Lagace, Amelia J. Eisch, Lee Anna Cunningham

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The purpose of this study was to ascertain the relative contribution of neural stem/progenitor cells (NSPCs) of the subventricular zone (SVZ) to lineages that repopulate the injured striatum following focal ischemia. We utilized a tamoxifen-inducible Cre/loxP system under control of the nestin promoter, which provides permanent YFP labeling of multipotent nestin1 SVZ-NSPCs prior to ischemic injury and continued YFP expression in all subsequent progeny following stroke. YFP reporter expression was induced in adult male nestin-CreERT2:R26R-YFP mice by tamoxifen administration (180 mg kg21, daily for 5 days). Fourteen days later, mice were subjected to 60-min transient middle cerebral artery occlusion (MCAO) and sacrificed at 2 days, 2 weeks, or 6 weeks post-MCAO for phenotypic fate mapping of YFP1 cells using lineage-specific markers. Migration of YFP1 cells from SVZ into the injured striatal parenchyma was apparent at 2 and 6 weeks, but not 2 days, post-MCAO. At 2 weeks post-MCAO, the average percent distribution of YFP1 cells within the injured striatal parenchyma was as follows: 10% Dcx1 neuroblasts, 15-20% oligodendrocyte progenitors, 59% GFAP1 astrocytes, and only rare NeuN1 postmitotic neurons. A similar phenotypic distribution was observed at 6 weeks, except for an increased average percentage of YFP1 cells that expressed Dcx1 (20%) or NeuN (5%). YFP1 cells did not express endothelial markers, but displayed unique anatomical relationships with striatal vasculature. These results indicate that nestin1 NSPCs within the SVZ mount a multilineage response to stroke that includes a gliogenic component more predominant than previously appreciated.

Original languageEnglish (US)
Pages (from-to)1610-1619
Number of pages10
JournalGLIA
Volume58
Issue number13
DOIs
StatePublished - Oct 1 2010

Keywords

  • Gliogenesis
  • Neurogenesis
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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