Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia

105

100

Neural progenitor cells in the subventricular zone (SVZ) of the lateral ventricular wall give rise to new neurons throughout rodent life. Ischemic stroke induces angiogenesis and neurogenesis. Using laser capture microdissection (LCM) in combination with microarrays containing approximately 400 known genes associated with stem cells and angiogenesis, we investigated gene profiles of SVZ cells in the adult mouse subjected to middle cerebral artery occlusion. Our data revealed that nonstroke SVZ cells expressed sets of genes that are important for neural progenitor cell proliferation, differentiation, and migration. In addition, stroke SVZ cells expressed many genes involved in neurogenesis during embryonic development but were not detected in nonstroke SVZ cells. Stroke upregulated genes were verified by real-time reverse transcriptase-polymerase chain reaction and immunostaining. These data indicate that adult SVZ cells recapture embryonic molecular signals after stroke and provide insight into the molecular mechanisms, which regulate the biological function of neural progenitor cells in the SVZ of adult rodent brain under physiological and stroke conditions.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stroke Induces Gene Profile Changes Associated with Neurogenesis and Angiogenesis in Adult Subventricular Zone Progenitor Cells

Liu¹,

Zhang²,

Zhang³

et al. 2006

105

100

“…The right middle cerebral artery (MCA) was occluded by placement of an embolus at the origin of the MCA (Zhang et al, 1997). Animals used for cumulative BrdU study were killed 7 days after stroke based on our previous studies showing neurogenesis in the SVZ with a peak at 7 days after stroke (Zhang et al, 2001b(Zhang et al, , 2004c.…”

Section: Animal Model Of Strokementioning

confidence: 99%

“…For BrdU immunostaining, DNA was first denatured by incubating coronal sections in 50% formamide 2 Â standard saline citrate at 651C for 2 h and then in 2 N HCl at 371C for 30 min (Zhang et al, 2001b). Sections were incubated with the anti-BrdU antibody (1:1000, Boehringer Mannheim, Indianapolis, IN, USA) overnight and then incubated with biotinylated secondary antibody (1:200, Vector, Burlingame, CA, USA) for 1 h. The reaction product was detected using 3 0 ,3 0 -diaminobenzidine-tetrahydrochloride (DAB, Sigma).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Reduction of the Cell Cycle Length by Decreasing G₁ Phase and Cell Cycle Reentry Expand Neuronal Progenitor Cells in the Subventricular Zone of Adult Rat after Stroke

Zhang¹,

Zhang²,

Lü

et al. 2005

A critical determinant of proliferation of progenitor cells is the duration of the cell division cycle. Stroke increases proliferation of progenitor cells in the subventricular zone (SVZ). Using cumulative and single S-phase labeling with 5-bromo-2 0 -deoxyuridine, we examined cell cycle kinetics of neural progenitor cells in the SVZ after stroke. In nonstroke rats, 20% of the SVZ cell population was proliferating. However, stroke significantly increased dividing cells up to 31% and these cells had a cell cycle length (T C ) of 15.3 h, significantly (P < 0.05) shorter than the 19 h Tc in nonstroke SVZ cells. Few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells were detected in the SVZ cells of nonstroke and stroke groups, suggesting that the majority of dividing cells in the SVZ do not undergo apoptosis. Cell cycle phase analysis revealed that stroke substantially shortened the length of the G 1 phase (9.6 h) compared with the G 1 phase of 12.6 h in nonstroke SVZ cells (P < 0.03). This reduction in G 1 contributes to stroke-induced reduction of T C because no significant changes were detected on the length of S, G 2 and M phases between two groups. Furthermore, compared with progenitor cells in nonstroke SVZ (10%), a greater proportion (14%) of progenitor cells in stroke SVZ reentered the cell cycle after mitosis (P < 0.05). These results show that an increase in proliferating progenitor cells in the SVZ contributes to stroke-induced neurogenesis and this increase is regulated by shortening the length of the cell cycle, decreasing the G 1 phase and increasing cell cycle reentry.

“…Cerebral ischemia increases neurogenesis, and the newly generated neurons in the SVZ migrate toward the ischemic boundary where angiogenesis takes place (Arvidsson et al, 2002;Jin et al, 2001;Parent et al, 2002;Zhang et al, 2001Zhang et al, , 2004. Blockage of stromal derived factor 1a (SDF-1a) and angiopoietin 1 in remodeling cerebral vessels attenuates neuroblast migration toward the cortical ischemic boundary (Ohab et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

Hua

Zhang

Wang

et al. 2007

228

176

Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.