Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Wang, Lei; Chopp, Michael; Hua, Teng; Bolz, Marianne; Francisco, Moniche Ãlvarez; Aluigi, Danielle Marie; Wang, Xin Li; Zhang, Rui Lan; Chrsitensen, Søren; Sager, Thomas N.; Szalad, Alexandra; Zhang, Zheng Gang

doi:10.1038/jcbfm.2010.200

Cited by 6 publications

(6 citation statements)

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“…30 Our recent study demonstrates that tumor necrosis factor alpha primes cerebral endothelial cells for erythropoietin-induced angiogenesis. 57 In addition, our in vitro study shows that EPO enhances VEGF secretion in neural progenitor cells through activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) signal-transduction pathways and that neural progenitor cells treated with EPO upregulate VEGFR2 expression in cerebral endothelial cells, which along with VEGF secreted by neural progenitor cells promotes angiogenesis. 56 In addition to its robust angiogenic effects, VEGF is capable of promoting hippocampal neurogenesis in the SVZ and SGZ in response to TBI.…”

Section: Discussionmentioning

confidence: 81%

Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats

Meng¹,

Xiong²,

Mahmood³

et al. 2011

JNS

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Object Delayed (24 hours post injury) treatment with erythropoietin (EPO) improves functional recovery following experimental traumatic brain injury (TBI). In this study, we tested whether therapeutic effects of delayed EPO treatment for TBI are dose-dependent in an attempt to establish an optimal dose paradigm for the delayed EPO treatment. Methods Experimental TBI was performed in anesthetized young adult male Wistar rats using a controlled cortical impact device. Sham animals underwent the same surgical procedure without injury. The animals (8 rats/group) received 3 intraperitoneal injections of EPO (0, 1000, 3000, 5000 or 7000 U/kg body weight, at 24, 48 and 72 hours) after TBI. Sensorimotor and cognitive functions were assessed using a modified neurological severity score and foot fault test, and Morris water maze tests, respectively. Animals were sacrificed 35 days after injury and brain sections stained for immunohistochemical analyses. Results Compared to the saline treatment, EPO treatment at doses from1000 to 7000 U/kg did not alter lesion volume but significantly reduced hippocampal neuron loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, and significantly improved sensorimotor function and spatial learning. The medium dose at 5000 U/kg exhibited a significant improvement in histological and functional outcomes compared with the lower or higher EPO dose groups. Conclusions These data demonstrate that delayed (24 hours post injury) treatment with EPO provides dose-dependent neurorestoration which may contribute to improved functional recovery after TBI, implying that application of an optimal dose of EPO is likely to increase successful preclinical and clinical trials for treatment of TBI.

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Section: Discussionmentioning

confidence: 81%

Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats

Meng¹,

Xiong²,

Mahmood³

et al. 2011

JNS

Self Cite

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“…To verify this possibility, we proceeded to test whether the enhancing effect of BV2 supernatant on HBMECs angiogenesis could be attenuated when the TNFR on HBMECs was blocked by specific neutralizing antibody. Studies have shown that signaling events induced by TNF‐α in endothelial cells, as well as in other cell types, are primarily dependent on the interaction of TNF‐α with TNF‐α receptor 1 (TNFR1) (Chainy et al, ; Al‐Lamki et al, ; Wang et al, ). Here, therefore, monoclonal antihuman TNFR1 neutralizing antibody was used to block the TNFR1 expressed on HBMECs.…”

Section: Resultsmentioning

confidence: 99%

Ephrin‐A3 and Ephrin‐A4 Contribute to Microglia‐Induced Angiogenesis in Brain Endothelial Cells

Liu

et al. 2014

The Anatomical Record

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The association of microglia with brain vasculature during development and the reduced brain vascular complexity in microglia-deficient mice suggest the role of microglia in cerebrovascular angiogenesis. However, the underlying molecular mechanism remains unclear. Here, using an in vitro angiogenesis model, we found the culture supernatant of BV2 microglial cells significantly enhanced capillary-like tube formation and migration of brain microvascular endothelial cells (BMECs). The expression of angiogenic factors, ephrin-A3 and ephrin-A4, were specifically upregulated in BMECs exposed to BV2-derived culture supernatant. Knockdown of ephrin-A3 and ephrin-A4 in BMECs by siRNA significantly attenuated the enhanced angiogenesis and migration of BMECs induced by BV2 supernatant. Our further results indicated that the ability of BV2 supernatant to promote endothelial angiogenesis was caused by the soluble tumor necrosis factor a (TNF-a) released from BV2 microglial cells. Moreover, the upregulations of ephrin-A3 and ephrin-A4 in BMECs in response to BV2 supernatant were effectively abolished by neutralization antibody against TNF-a and TNF receptor 1, respectively. The present study provides evidence that microglia upregulates endothelial ephrin-A3 and ephrin-A4 to facilitate in vitro angiogenesis of brain endothelial cells, which is mediated by microglia-released TNF-a.

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“…In addition, the proinflammatory cytokines such as TNF-α, MCP-1, and SDF-1 also can affect angiogenesis. The research has shown that the interaction of TNF-α with TNF receptor 1 can amplify the effect of erythropoietininduced angiogenesis by upregulation of the erythropoietin receptor [86]. Significantly, a high dose of TNF inhibits angiogenesis, but the pericytes can enhance angiogenesis and overcome the inhibition of angiogenesis induced by a high dose of TNF [79].…”

Section: Exosomes In Crosstalk Betweenmentioning

confidence: 99%

Exosome in Crosstalk between Inflammation and Angiogenesis: A Potential Therapeutic Strategy for Stroke

Cun

Jin

et al. 2022

Mediators of Inflammation

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The endothelial dysfunction, associated with inflammation and vascular permeability, remains the key event in the pathogenesis of cerebral ischemic stroke. Angiogenesis is essential for neuroprotection and neural repair following stroke. The neuroinflammatory reaction plays a vital role in stroke, and inhibition of inflammation contributes to establishing an appropriate external environment for angiogenesis. Exosomes are the heterogeneous population of extracellular vesicles which play critical roles in intercellular communication through transmitting various proteins and nucleic acids to nearby and distant recipient cells by body fluids and circulation. Recent reports have shown that exosomal therapy is a valuable and potential treatment strategy for stroke. In this review, we discussed the exosomes in complex interaction mechanisms of angiogenesis and inflammation following stroke as well as the challenges of exosomal studies such as secretion, uptake, modification, and application.

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Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Cited by 6 publications

References 0 publications

Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats

Dose-dependent neurorestorative effects of delayed treatment of traumatic brain injury with recombinant human erythropoietin in rats

Ephrin‐A3 and Ephrin‐A4 Contribute to Microglia‐Induced Angiogenesis in Brain Endothelial Cells

Exosome in Crosstalk between Inflammation and Angiogenesis: A Potential Therapeutic Strategy for Stroke

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