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Dev Neurosci 2010;32:101–113

Altered Fate of Subventricular Zone Progenitor Cells and Reduced Neurogenesis following Neonatal Stroke

Spadafora R.a · Gonzalez F.F.a, b · Derugin N.c · Wendland M.d · Ferriero D.a, b · McQuillen P.a, b
Departments of aNeurology, bPediatrics, cNeurosurgery, and dRadiology, University of California, San Francisco, Calif., USA
email Corresponding Author

 goto top of outline Key Words

  • Ischemia
  • Neonate
  • Stem cells
  • Neurogenesis

 goto top of outline Abstract

Objective: To investigate the effects of neonatal stroke on progenitor cells lining the lateral ventricles. Methods: Intraventricular injection of replication-incompetent green fluorescent protein (GFP)-expressing lentivirus was performed in postnatal day 1 (P1) rats to specifically label radial glia/type B neural stem cells and ependymal cells of the lateral ventricle. A subset of animals was exposed to transient middle cerebral artery occlusion (MCAO) at P7, with mild or moderate injury confirmed by diffusion-weighted MRI and histology. Newborn cells were identified by GFP expression, location and expression of cell type-specific markers in the striatum, cortex and olfactory bulb using confocal microscopy and systematic random sampling. Results: Three weeks lentiviral GFP transduction of cells in the lateral ventricle, abundant GFP-expressing neurons and glia were identified in the rostral migratory stream, olfactory bulb and striatum as expected from labeling the subventricular zone (SVZ) type B neural stem cell lineage. Two weeks following mild or severe focal stroke at P7, no GFP-expressing neurons were detected in striatum or cortex although some single-labeled doublecortin+ immature neurons were detected in the penumbra. The densities of GFP+/ glial fibrillary acidic protein (GFAP)+ astrocytes and GFP+/O4+ oligodendrocytes were reduced in the striatum following MCAO (4.8 ± 1.02 vs. 2.5 ± 0.4 cells/high-power field, HPF; p = 0.005; 2.8± 1 vs. 0.5 ± 0.2 cells/HPF, p = 0.008). Furthermore, there was a reduction of GFP+ cells in the olfactory bulb following MCAO (58.8 ± 14.9 vs. 19.6 ± 5.4 cells/HPF, p = 0.025). Finally, there was an increased percentage of GFP+/GFAP+ cells (70 vs. 50%), with a decreased proportion of GFP+/O4+ cells (14 vs. 30%) in injured animals. Conclusion: Neurogenesis originating from cells of the lateral ventricle, including SVZ type B cells, is significantly reduced following neonatal stroke. Furthermore, neonatal stroke disrupts gliogenesis in the striatum, decreasing overall numbers of new glia and shifting the population towards astrocytes.

Copyright © 2010 S. Karger AG, Basel

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 goto top of outline Author Contacts

Prof. Donna M. Ferriero, MD
University of California, San Francisco
521 Parnassus Avenue, Rm C215
San Francisco, CA 94143-0663 (USA)
Tel. +1 415 502 5820, Fax +1 415 502 5821, E-Mail donna.ferriero@ucsf.edu

 goto top of outline Article Information

Received: July 27, 2009
Accepted after revision: January 21, 2010
Published online: May 4, 2010
Number of Print Pages : 13
Number of Figures : 5, Number of Tables : 0, Number of References : 43
Additional supplementary material is available online - Number of Parts : 1

 goto top of outline Publication Details

Developmental Neuroscience

Vol. 32, No. 2, Year 2010 (Cover Date: July 2010)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE

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