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

84 Citations (Scopus)

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 2010

Fingerprint

Lateral Ventricles
Middle Cerebral Artery Infarction
Brain Ischemia
Corpus Striatum
Neural Stem Cells
Nestin
Stem Cells
Tamoxifen
Stroke
Oligodendroglia
Cell Lineage
Astrocytes
Cell Movement
Ischemia
Neurons
Wounds and Injuries

Keywords

  • Gliogenesis
  • Neurogenesis
  • Stroke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. / Li, Lu; Harms, Kate M.; Ventura, P. Britten; Lagace, Diane C.; Eisch, Amelia J.; Cunningham, Lee Anna.

In: GLIA, Vol. 58, No. 13, 10.2010, p. 1610-1619.

Research output: Contribution to journalArticle

Li, Lu ; Harms, Kate M. ; Ventura, P. Britten ; Lagace, Diane C. ; Eisch, Amelia J. ; Cunningham, Lee Anna. / Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. In: GLIA. 2010 ; Vol. 58, No. 13. pp. 1610-1619.
@article{a0dbc754db3e4fa49db749d9d0012d8e,
title = "Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic",
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.",
keywords = "Gliogenesis, Neurogenesis, Stroke",
author = "Lu Li and Harms, {Kate M.} and Ventura, {P. Britten} and Lagace, {Diane C.} and Eisch, {Amelia J.} and Cunningham, {Lee Anna}",
year = "2010",
month = "10",
doi = "10.1002/glia.21033",
language = "English (US)",
volume = "58",
pages = "1610--1619",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "13",

}

TY - JOUR

T1 - Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic

AU - Li, Lu

AU - Harms, Kate M.

AU - Ventura, P. Britten

AU - Lagace, Diane C.

AU - Eisch, Amelia J.

AU - Cunningham, Lee Anna

PY - 2010/10

Y1 - 2010/10

N2 - 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.

AB - 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.

KW - Gliogenesis

KW - Neurogenesis

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=77957376758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957376758&partnerID=8YFLogxK

U2 - 10.1002/glia.21033

DO - 10.1002/glia.21033

M3 - Article

VL - 58

SP - 1610

EP - 1619

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 13

ER -