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VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain
- Source :
- The Journal of clinical investigation. 104(11)
- Publication Year :
- 1999
-
Abstract
- VEGF is mitogenic, angiogenic, and a potent mediator of vascular permeability. VEGF causes extravasation of plasma protein in skin bioassays and increases hydraulic conductivity in isolated perfused microvessels. Reduced tissue oxygen tension triggers VEGF expression, and increased protein and mRNA levels for VEGF and its receptors (Flt-1, Flk-1/KDR) occur in the ischemic rat brain. Brain edema, provoked in part by enhanced cerebrovascular permeability, is a major complication in central nervous system pathologies, including head trauma and stroke. The role of VEGF in this pathology has remained elusive because of the lack of a suitable experimental antagonist. We used a novel fusion protein, mFlt(1-3)-IgG, which sequesters murine VEGF, to treat mice exposed to transient cortical ischemia followed by reperfusion. Using high-resolution magnetic resonance imaging, we found a significant reduction in volume of the edematous tissue 1 day after onset of ischemia in mice that received mFlt(1-3)-IgG. 8-12 weeks after treatment, measurements of the resultant infarct size revealed a significant sparing of cortical tissue. Regional cerebral blood flow was unaffected by the administration of mFlt(1-3)-IgG. These results demonstrate that antagonism of VEGF reduces ischemia/reperfusion-related brain edema and injury, implicating VEGF in the pathogenesis of stroke and related disorders.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Recombinant Fusion Proteins
Central nervous system
Ischemia
Vascular permeability
Brain Edema
Endothelial Growth Factors
Article
Brain Ischemia
Brain ischemia
Mice
Proto-Oncogene Proteins
medicine
Animals
Stroke
Ligation
Lymphokines
Vascular Endothelial Growth Factor Receptor-1
business.industry
Histocytochemistry
Vascular Endothelial Growth Factors
Brain
Receptor Protein-Tyrosine Kinases
General Medicine
medicine.disease
Magnetic Resonance Imaging
Extravasation
Mice, Inbred C57BL
medicine.anatomical_structure
Cerebral blood flow
Regional Blood Flow
Immunoglobulin G
Reperfusion Injury
Immunology
business
Reperfusion injury
Injections, Intraperitoneal
Subjects
Details
- ISSN :
- 00219738
- Volume :
- 104
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical investigation
- Accession number :
- edsair.doi.dedup.....dfc7d5409b54479590f4db54acd898d8