| Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9. | |
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MedLine Citation:
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PMID: 19471278 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cerebral venous hypertension (VH) and angiogenesis are implicated in the pathogenesis of brain arteriovenous malformation and dural arteriovenous fistulae. We studied the association of VH and angiogenesis using a mouse brain VH model. Sixty mice underwent external jugular vein and common carotid artery (CCA) anastomosis (VH model), CCA ligation, or sham dissection (n=20). Hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and stromal-cell-derived factor-1alpha (SDF-1alpha) expression, and matrix metalloproteinase (MMP) activity were analyzed. We found VH animals had higher (P<0.05) sagittal sinus pressure (8+/-1 mm Hg) than control groups (1+/-1 mm Hg). Surface cerebral blood flow and mean arterial pressure did not change. Hypoxia-inducible factor-1alpha, VEGF, and SDF-1alpha expression increased (P<0.05). Neutrophils and MMP-9 activity increased 10-fold 1 day after surgery, gradually decreased afterward, and returned to baseline 2 weeks after surgery. Macrophages began to increase 3 days after surgery (P<0.05), which coincided with the changes in SDF-1alpha expression. Capillary density in the parasagittal cortex increased 17% compared with the controls. Our findings suggest that mild nonischemic VH results in a pro-angiogenic stage in the brain by upregulating HIF-1 and its downstream targets, VEGF and SDF-1alpha, increasing leukocyte infiltration and MMP-9 activity. |
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Authors:
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Peng Gao; Yiqian Zhu; Feng Ling; Fanxia Shen; Brian Lee; Rodney Allanigue Gabriel; Qi Hao; Guo-Yuan Yang; Hua Su; William L Young |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-27 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 29 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-31 Completed Date: 2009-08-13 Revised Date: 2011-08-23 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1482-90 Citation Subset: IM |
Affiliation:
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Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, California 94110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Flow Velocity / physiology Blotting, Western Cerebral Veins / metabolism, pathology* Cerebrovascular Circulation / physiology Chemokine CXCL12 / biosynthesis, genetics Disease Models, Animal Enzyme-Linked Immunosorbent Assay Gene Expression Regulation / drug effects* Hypertension / genetics, metabolism, pathology* Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis* Immunohistochemistry Macrophages / pathology Male Matrix Metalloproteinase 9 / biosynthesis*, genetics Mice Mice, Inbred C57BL Neovascularization, Pathologic / enzymology, genetics*, metabolism, pathology Neutrophil Infiltration Neutrophils / enzymology* Vascular Endothelial Growth Factor A / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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NS044145/NS/NINDS NIH HHS; NS27713/NS/NINDS NIH HHS; P01 NS044155-05/NS/NINDS NIH HHS; R01 NS027713-17/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL12; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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