title: Altered fate of subventricular zone progenitor cells and reduced neurogenesis following neonatal stroke.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94143-0663, USA.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Spadafora
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Gonzalez
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: Michael
authors.initials: M
authors.lastname: Wendland
authors.forename: Donna
authors.initials: D
authors.lastname: Ferriero
authors.forename: Patrick
authors.initials: P
authors.lastname: McQuillen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D000089662:Doublecortin Protein; D004805:Ependyma / Q000166:cytology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013234:Stem Cells / Q000502:physiology*; D020521:Stroke / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D049452:Green Fluorescent Proteins
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