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Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic
Author(s) -
Li Lu,
Harms Kate M.,
Ventura P. Britten,
Lagace Diane C.,
Eisch Amelia J.,
Cunningham Lee Anna
Publication year - 2010
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21033
Subject(s) - neun , subventricular zone , nestin , biology , neuroblast , gliogenesis , microbiology and biotechnology , progenitor cell , neurogenesis , oligodendrocyte , stem cell , neural stem cell , neuroscience , immunology , central nervous system , myelin , immunohistochemistry
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 nestin + 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‐CreER T2 :R26R‐YFP mice by tamoxifen administration (180 mg kg −1 , 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 YFP + cells using lineage‐specific markers. Migration of YFP + 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 YFP + cells within the injured striatal parenchyma was as follows: 10% Dcx + neuroblasts, 15–20% oligodendrocyte progenitors, 59% GFAP + astrocytes, and only rare NeuN + postmitotic neurons. A similar phenotypic distribution was observed at 6 weeks, except for an increased average percentage of YFP + cells that expressed Dcx + (20%) or NeuN (5%). YFP + cells did not express endothelial markers, but displayed unique anatomical relationships with striatal vasculature. These results indicate that nestin + NSPCs within the SVZ mount a multilineage response to stroke that includes a gliogenic component more predominant than previously appreciated. © 2010 Wiley‐Liss, Inc.