Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery

Kusaka, Noboru; Sugiu, Kenji; Tokunaga, Koji; Katsumata, Atsushi; Nishida, Akihiko; Namba, Katsunari; Hamada, Hirofumi; Nakashima, Hiroyuki; Date, Isao

doi:10.3171/jns.2005.103.5.0882

Cited by 45 publications

(39 citation statements)

References 52 publications

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“…102 PlGF, a ligand for VEGFR and neuropilin-1 is thought to simultaneously regulate angiogenesis and neurogenesis after stroke. 103 Functional recovery following MCAO in a rat model of stroke was elevated coincident with enhanced neurogenesis and angiogenesis after an adenovirus-mediated gene transfer of heparin-binding EGF-like growth factor (HB-EGF).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms and targets for angiogenic therapy after stroke

Navaratna

Guo

Arai

et al. 2009

Cell Adhesion & Migration

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Stroke remains a major health problem worldwide, and is the leading cause of serious long-term disability. Recent findings now suggest that strategies to enhance angiogenesis after focal cerebral ischemia may provide unique opportunities to improve clinical outcomes during stroke recovery. In this mini-review, we survey emerging mechanisms and potential targets for angiogenic therapies in brain after stroke. Multiple elements may be involved, including growth factors, adhesion molecules and progenitor cells. Furthermore, cross talk between angiogenesis and neurogenesis may also provide additional substrates for plasticity and remodeling in the recovering brain. A better understanding of the molecular interplay between all these complex pathways may lead to novel therapeutic avenues for tackling this difficult disease.

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Section: Discussionmentioning

confidence: 99%

Mechanisms and targets for angiogenic therapy after stroke

Navaratna

Guo

Arai

et al. 2009

Cell Adhesion & Migration

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“…However, unlike tumor angiogenesis, the role of VEGF may be minimal, as evidenced by variable levels of VEGF in the cerebrospinal fluid. [32][33][34][35][36][37] In addition IL-8, platelet-derived growth factor, endothelial growth factor, and transforming growth factor-␤ were not elevated in the cerebrospinal fluid, suggesting a different signaling pathway and mechanism of angiogenesis. 3 Therefore, our findings were not surprising to us.…”

Section: Rafat Et Al Increased Cepc In Patients With Moyamoya Diseasementioning

confidence: 99%

Increased Levels of Circulating Endothelial Progenitor Cells in Patients With Moyamoya Disease

Rafat

Beck

Peña-Tapia

et al. 2009

Stroke

102

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Background and Purpose-Chronic cerebral ischemia leads to higher risk for strokes attributable to insufficient collateralization, resulting from inadequate capacity for arteriogenesis and angiogenesis. Patients with Moyamoya disease (MMD) have similar transient ischemic attack frequencies compared to patients with chronic cerebral ischemia with other etiologies, but a strong capacity for arteriogenesis and angiogenesis. The mechanisms involved in the upregulation of the arteriogenesis and angiogenesis in MMD still remain unknown. In the present study we investigated if circulating endothelial progenitor cells are increasingly mobilized during MMD. Methods-Twenty MMD patients, 8 patients with atherosclerotic cerebrovascular disease, and 15 healthy individuals were included in this study. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and circulating endothelial progenitor cells were characterized by triple staining using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor and granulocytemacrophage colony-stimulating factor were determined by enzyme-linked immunosorbent assay. Results-In MMD patients the number of circulating endothelial progenitor cells was significantly higher than in atherosclerotic cerebrovascular disease patients (PϽ0.002) and healthy controls (PϽ0.0001). Serum vascular endothelial growth factor concentrations in MMD patients and in atherosclerotic cerebrovascular disease patients were significantly higher compared to those in healthy controls (PϽ0.0001). Similar findings were observed for granulocytemacrophage colony-stimulating factor. An inverse correlation between circulating endothelial progenitor cell numbers and serum levels of vascular endothelial growth factor (rϭϪ0.53; PϽ0,02) was found in the MMD group. Conclusion-Our results show increased circulating endothelial progenitor cell numbers in MMD, which may play a role in the increased arteriogenesis and angiogenesis in MMD. Moreover, our results suggest that increased circulating endothelial progenitor cell mobilization in MMD may not be entirely mediated by vascular endothelial growth factor or granulocyte-macrophage colony-stimulating factor. (Stroke. 2009;40:432-438.)

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“…3,11,12,16,23) Many experimental studies on VEGF administration have shown effectiveness against brain ischemia in various models. 9,10,15,17,19,21,22,[24][25][26] VEGF was administered by various methods, including VEGF protein, 24) plasmid-containing VEGF complementary deoxyribonucleic acid (cDNA), 13) adeno-associated viral vector-mediated VEGF cDNA, 15,21) VEGF gene-transformed bone marrow stromal cells engineered with a herpes simplex virus, 17) encapsulated transformed kidney cellsproducing VEGF, 25) and others. We previously reported that administration of plasmid human VEGF (phVEGF) combined with indirect vasoreconstructive surgery significantly increased angiogenesis in the rat ischemia model.…”

Section: Introductionmentioning

confidence: 99%

“…We previously reported that administration of plasmid human VEGF (phVEGF) combined with indirect vasoreconstructive surgery significantly increased angiogenesis in the rat ischemia model. 13) VEGF also increases vascular permeability leading to brain edema, 9,15,20,25,26) so might cause adverse effects including brain edema, resulting in complications related to the clinical use of phVEGF. 15,20,25) Therefore, evaluation of the most effective but safe dose of phVEGF is critical point for clinical application of phVEGF in human patients with brain ischemia.…”

Section: Introductionmentioning

confidence: 99%

Optimal Dose of Plasmid Vascular Endothelial Growth Factor for Enhancement of Angiogenesis in the Rat Brain Ischemia Model

Katsumata

Sugiu

Tokunaga

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Vascular endothelial growth factor (VEGF) administration has recently been assessed as a therapeutic strategy for ischemic diseases including brain ischemia because of its angiogenic effect. However, VEGF also causes detrimental adverse effects by increasing vascular permeability. This study examined whether plasmid human VEGF (phVEGF) administration induced angiogenic effects in the rat brain ischemia model caused by permanent ligation of both common carotid arteries, and investigated the occurrence of adverse effects. Administration of various doses (0-200 mg) of phVEGF in the temporal muscle was followed by encephalo-myo-synangiosis. Thirty days after treatment, the numbers and areas of capillaries per field in the extracted brains were analyzed with the National Institutes of Health Image software program. The maximal angiogenic effect occurred with a 100 mg dose of phVEGF in the numbers and areas of capillaries in the VEGF-treated brains. Histological examination showed no apparent adverse effects in the brain parenchyma even at the highest administration dose (200 mg) of phVEGF. The maximal angiogenic effect at the optimal dose of phVEGF can be considered under the threshold to cause serious adverse effects in the rat brain.

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Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery

Cited by 45 publications

References 52 publications

Mechanisms and targets for angiogenic therapy after stroke

Mechanisms and targets for angiogenic therapy after stroke

Increased Levels of Circulating Endothelial Progenitor Cells in Patients With Moyamoya Disease

Optimal Dose of Plasmid Vascular Endothelial Growth Factor for Enhancement of Angiogenesis in the Rat Brain Ischemia Model

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