Time- and cell type-specific induction of platelet-derived growth factor receptor-β during cerebral ischemia
During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PD...
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Published in | Brain research. Molecular brain research. Vol. 113; no. 1; pp. 44 - 51 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
12.05.2003
Elsevier |
Subjects | |
Online Access | Get full text |
ISSN | 0169-328X 1872-6941 |
DOI | 10.1016/S0169-328X(03)00085-8 |
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Abstract | During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-β system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-β are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-β expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-β mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-β on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-β as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition. |
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AbstractList | During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-beta system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-beta are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-beta expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-beta mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-beta on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-beta as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition. During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-β system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-β are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-β expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-β mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-β on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-β as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition. During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-beta system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-beta are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-beta expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-beta mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-beta on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-beta as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition.During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-beta system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-beta are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-beta expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-beta mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-beta on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-beta as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition. |
Author | Petit, Edwige Schaper, Wolfgang Valable, Samuel Kostin, Sawa Renner, Oliver Tsimpas, Asterios Marti, Hugo H. |
Author_xml | – sequence: 1 givenname: Oliver surname: Renner fullname: Renner, Oliver email: orenner@cnio.es organization: Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany – sequence: 2 givenname: Asterios surname: Tsimpas fullname: Tsimpas, Asterios organization: Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany – sequence: 3 givenname: Sawa surname: Kostin fullname: Kostin, Sawa organization: Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany – sequence: 4 givenname: Samuel surname: Valable fullname: Valable, Samuel organization: UMR 6551-CNRS, IFR47-Neuro-Imagerie Fonctionelle, Bd. Henri Becquerel, F-14074 Caen, France – sequence: 5 givenname: Edwige surname: Petit fullname: Petit, Edwige organization: UMR 6551-CNRS, IFR47-Neuro-Imagerie Fonctionelle, Bd. Henri Becquerel, F-14074 Caen, France – sequence: 6 givenname: Wolfgang surname: Schaper fullname: Schaper, Wolfgang organization: Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany – sequence: 7 givenname: Hugo H. surname: Marti fullname: Marti, Hugo H. organization: Department of Molecular Cell Biology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany |
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Keywords | Disorders of the nervous systems Angiogenesis Pericyte Edema Stroke Receptor tyrosine kinase Vascular permeability Nervous system diseases Rodentia Cardiovascular disease Cerebral disorder Vascular disease Vertebrata Experimental disease Growth factor receptor Mammalia Ischemia Mouse Animal Central nervous system disease Cerebrovascular disease Platelet derived growth factor Brain (vertebrata) |
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SubjectTerms | Angiogenesis Animals Biological and medical sciences Brain - blood supply Brain - metabolism Brain - physiopathology Brain Ischemia - genetics Brain Ischemia - metabolism Cell Differentiation - genetics Cerebral Infarction - genetics Cerebral Infarction - metabolism Edema Endothelium, Vascular - metabolism Fluorescent Antibody Technique Medical sciences Mice Mice, Inbred Strains Neovascularization, Physiologic - physiology Neurology Pericyte Pericytes - metabolism Platelet Endothelial Cell Adhesion Molecule-1 - metabolism Platelet-Derived Growth Factor - metabolism Reaction Time - genetics Receptor tyrosine kinase Receptor, Platelet-Derived Growth Factor beta - genetics Receptor, Platelet-Derived Growth Factor beta - metabolism Recovery of Function - physiology RNA, Messenger - metabolism Stroke Up-Regulation - genetics Vascular diseases and vascular malformations of the nervous system Vascular permeability |
Title | Time- and cell type-specific induction of platelet-derived growth factor receptor-β during cerebral ischemia |
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