Neural Stem/Progenitor Cells Promote Endothelial Cell Morphogenesis and Protect Endothelial Cells against Ischemia via HIF-1α-Regulated VEGF Signaling

Roitbak, Tamara; Li, Lü; Cunningham, Lee Anna

doi:10.1038/jcbfm.2008.38

Cited by 90 publications

(122 citation statements)

References 40 publications

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“…Although several signaling mechanisms may be activated under such conditions, many of the hypoxia effects on DAergic neuron development in culture have been related to increased HIF stabilization. Proliferating mesencephalic progenitors constitutively express HIF1a in normoxic conditions, as previously reported for neural stem cells (Roitbak et al, 2008), and these levels decrease after differentiation. However, treatment with 5-HD or Apo did not affect HIF1a levels in the cultures, suggesting that HIF did not have a major effect on the observed results.…”

Section: Discussionsupporting

confidence: 77%

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Rodríguez‐Pallares

Joglar

Díaz-Ruiz

et al. 2010

Developmental Dynamics

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Reactive oxygen species signaling has been suggested to regulate stem cell development. In the present study, we treated neurospheres of rat mesencephalic precursors with inhibitors of the NADPH oxidase complex and mitochondrial ATP-sensitive potassium (mitoKATP) channel blockers during the proliferation and/or the differentiation periods to study the effects on generation of dopaminergic neurons. Treatment with low doses (100 or 250 mM) of the NADPH inhibitor apocynin during the proliferation period increased the generation of dopaminergic neurons. However, higher doses (1 mM) were necessary during the differentiation period to induce the same effect. Treatment with general (glibenclamide) or mitochondrial (5-hydroxydecanoate) KATP channel blockers during the proliferation and differentiation periods increased the number of dopaminergic neurons. Furthermore, neither increased proliferation rate nor apoptosis had a major role in the observed increase in generation of dopaminergic neurons, which suggests that the redox state is able to regulate differentiation of precursors into dopaminergic neurons. Developmental Dynamics 239:3247-3259,

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Section: Discussionsupporting

confidence: 77%

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Rodríguez‐Pallares

Joglar

Díaz-Ruiz

et al. 2010

Developmental Dynamics

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“…[36][37][38] In hypoxia, the transcription of VEGF is increasingly regulated by HIF-1α, one of the most potent regulators. 39,40) In conjunction with these findings, our studies showed that HJDTaq and HJDTet increased the expression of HIF-1α and VEGF. We further showed that one of the VEGF receptors, Flk-1, was also increased in hypoxic/ischemic conditions, as previously reported.…”

Section: Discussionsupporting

confidence: 70%

Huanglian-Jie-Du-Tang Extract Protects against Chronic Brain Injury after Focal Cerebral Ischemia via Hypoxia-Inducible-Factor-1α-Regulated Vascular Endothelial Growth Factor Signaling in Mice

Huang

Jiang

et al. 2012

Biological & Pharmaceutical Bulletin

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Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula which is widely used clinically. In this study, we investigated the effects of an aqueous (HJDTaq) and an ethanolic (HJDTet) extract of HJDT on chronic brain injury after focal cerebral ischemia in mice. The ischemia was induced by occlusion of the right middle cerebral artery for 30 min. HJDTaq (4 g/kg) and HJDTet (200, 400, 800 mg/kg) were orally administered for 21 d from day 7 before ischemia to day 14 after ischemia. The survival rate decreased to less than 50% at 35 d after ischemia. HJDTet at 400 mg/kg increased the survival rate. HJDTaq (4 g/kg) and HJDTet (400, 800 mg/kg) significantly attenuated the neurological dysfunction, brain atrophy and infarct volume after ischemia. There were few cells positive for CD31, hypoxia-inducible-factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and Flk-1 in the sham control. After ischemia, the number increased. HJDTaq (4 g/kg) and HJDTet (400 or 800 mg/kg) further increased the numbers of CD31, HIF-1α, VEGF and Flk-1-positive cells in the ischemic hemisphere. We conclude that HJDTaq and HJDTet have neuroprotective effects on chronic brain injury after focal cerebral ischemia and lead to accelerated angiogenesis by HIF-1α-regulated VEGF signaling.

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“…It is known that nestin + and DCX + cells can protect endothelial cells from cell death during ischemia. 34 It is possible that SDF-1α indirectly protects endothelial cells and stabilizes brain vasculature by promoting the proliferation and migration of NPCs.…”

Section: June 2014mentioning

confidence: 99%

Postacute Stromal Cell–Derived Factor-1α Expression Promotes Neurovascular Recovery in Ischemic Mice

Huang

et al. 2014

Stroke

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A lthough the majority of patients with ischemic stroke survive with timely treatment in the acute phase, many still experience various long-term neurological deficits. 1 One of the obstacles to neurobehavioral recovery is limited spontaneous neurogenesis and angiogenesis in the postacute phase. Therapeutics that target the postacute phase with a wider treatment window would help improve functional recovery after stroke.Stromal cell-derived factor-1 (SDF-1), also called C-X-C motif chemokine ligand 12, functions by interacting with its receptor CXCR4, which is found on the cell surface of leucocytes and various kinds of stem cells.2-7 Previously, we have shown that blocking SDF-1/CXCR4 interaction suppresses inflammatory responses and reduces brain infarction in the acute phase of ischemic stroke. 8,9 In addition, CXCR4 gene transfer into the heart before myocardial ischemia enhances ischemia-reperfusion injury and increases the influx of inflammatory cells. 10 These results suggest that SDF-1 functions mainly as an inflammatory initiator during the acute phase of ischemia. However, the function of SDF-1 during the postacute phase of ischemia is still unknown.It is noteworthy that SDF-1 plays an important role during the development of the central nervous system and has a strong modulation effect on neurons, interneurons, and granule cells. [11][12][13][14][15] It is now recognized that SDF-1 regulates the development of nervous tissue, particularly because of its effects on cell migration and axon guidance.16 SDF-1 is also essential to the development of vasculature by recruiting Background and Purpose-Acute interventions of stroke are often challenged by a narrow treatment window. In this study, we explore treatments in the postacute phase of stroke with wider windows of opportunity. We investigated the effects of stromal cell-derived factor (SDF-1α) in neurovascular recovery during the postacute phase and downstream signaling pathways, underlying SDF-1α-mediated neurovascular recovery. Methods-Adult male Institute of Cancer Research (ICR) mice underwent middle cerebral artery occlusion. One week after middle cerebral artery occlusion, the animals received stereotactic injection of adenoassociated virus (AAV) carrying SDF-1α gene as treatment or AAV-green fluorescent protein as control and were monitored for 5 weeks. Neurobehavioral outcomes were evaluated, and brain atrophy was measured. Neurogenesis and angiogenesis were examined. The proliferation and migration of neural progenitor cells were evaluated. Downstream pathways of SDF-1α were investigated. Inflammatory response was monitored. Results-Neurobehavioral outcomes were improved, and brain atrophy was greatly reduced for ≤5 weeks in AAV-SDF-1α groups when compared with the control. SDF-1 receptor CXCR4 was upregulated and colocalized with neural and endothelial progenitor cells. Li et al SDF-1 Promotes Neurobehavioral Recovery 1823circulating endothelial progenitor cells (EPCs) involved in angiogenesis. [17][18][19][20][21][22] It is possible that SDF...

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Neural Stem/Progenitor Cells Promote Endothelial Cell Morphogenesis and Protect Endothelial Cells against Ischemia via HIF-1α-Regulated VEGF Signaling

Cited by 90 publications

References 40 publications

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Effect of inhibitors of NADPH oxidase complex and mitochondrial ATP‐sensitive potassium channels on generation of dopaminergic neurons from neurospheres of mesencephalic precursors

Huanglian-Jie-Du-Tang Extract Protects against Chronic Brain Injury after Focal Cerebral Ischemia via Hypoxia-Inducible-Factor-1α-Regulated Vascular Endothelial Growth Factor Signaling in Mice

Postacute Stromal Cell–Derived Factor-1α Expression Promotes Neurovascular Recovery in Ischemic Mice

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