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

Abstract

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.

Mobilization of Neural Stem Cells and Generation of New Neurons in 6-OHDA–lesioned Rats by Intracerebroventricular Infusion of Liver Growth Factor

“…The first targets of LGF in liver are portal vein endothelial cells (Díaz-Gil et al 2003). Endothelial cells stimulate the selfrenewal of NSCs, as well as neuronal differentiation of neural progenitors through the production of soluble factors and direct contact (Palmer et al 2000;Jin et al 2002;Doetsch 2003;Shen et al 2004;Li et al 2006;Gama Sosa et al 2007;Teng et al 2008;Guo et al 2008). In the striatum of ICV-LGF-infused animals, ?20% of the BrdU-positive cells were located near the blood vessels, but only 5% of these cells showed the morphology of endothelial cells, suggesting that this cell type is not the main target for LGF in our experimental model of PD.…”

“…Moreover, LGF stimulates the synthesis of vascular endothelial growth factor (VEGF) and its receptors in testis (Martín-Hidalgo et al 2007). Considering the increasing number of reports that relate endothelial stimulation to neurogenesis (Palmer et al 2000;Doetsch 2003;Shen et al 2004;Teng et al 2008;Guo et al 2008), we wondered whether LGF could promote the generation of new neurons in a known model of PD in rats. In this study, we report that ICV infusion of LGF stimulates the proliferation and migration of SVZ-derived neuronal precursors into the denervated striatum of 6-OHDA-lesioned rats.…”

Early Inhibition of MMP Activity in Ischemic Rat Brain Promotes Expression of Tight Junction Proteins and Angiogenesis During Recovery

“…Angiogenesis provides critical neurovascular substrates for remodeling after stroke by generating new vessels necessary for neurogenesis and synaptogenesis. 1,[24][25][26] Factors released by endothelial cells in vitro trigger neural stem cell proliferation and angiogenesis, contributing to functional recovery. 27 We found that some vessels remain in the lesion areas up to 7 days after reperfusion, which could provide the cellular basis to trigger angiogenesis.…”

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

“…The vasculature is regarded as a key element, especially in the adult SVZ [3], and ECs are thought to contribute importantly to this vascular microenvironment [4,5]. In support of this viewpoint, coculture experiments have shown that ECs increase proliferation of NSPCs derived from the adult SVZ, thereby promoting neurogenesis [6,7]. However, accumulating evidence indicates that NSPCs are present in many parts of the adult brain, including the cortex [8][9][10], subcortical white matter [11], and spinal cord [12][13][14]; that is, outside conventional neurogenic zones, including SVZ and SGZ.…”