(Stroke. 1996;27:1865-1873.)
© 1996 American Heart Association, Inc.
Articles |
VEGF and flt
Expression Time Kinetics in Rat Brain Infarct
the Department of Neurosurgery, Neurological Institute, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Correspondence to Kiyonobu Ikezaki, MD, PhD, Department of Neurosurgery, Neurological Institute, Kyushu University Faculty of Medicine, Fukuoka 812-82, Japan. E-mail nobu@ns.med.kyushu-u.ac.jp.
Background and Purpose Vascular endothelial growth/vascular permeability factor (VEGF) is a candidate for an angiogenic and hyperpermeability inducing factor in an infarct because it is a secretable mitogen specific for endothelial cells and is upregulated by hypoxia. Our study attempts to clarify the chronological expression of VEGF and its receptor (flt) system in experimental cerebral infarction.
Methods With the use of a reproducible middle cerebral artery occlusion model in rats, VEGF expression was identified by Western blotting with anti-VEGF antibody. The chronological expression of the VEGF/flt system was analyzed semiquantitatively by immunohistochemical means in infarcts with different time courses from 3 hours to 3 weeks.
Results VEGF and flt were expressed exclusively in the ischemic brain. The bands obtained on the immunoblot at 38 and 45 kD are related to those of VEGF121 and VEGF165 isoforms. Macrophages, neurons, and glial cells chronologically expressed VEGF immunoreactivity in a different fashion. Both VEGF (bound) and flt were detected in endothelial cells along with the development of angiogenesis.
Conclusions In the ischemic brain the macrophages, neurons, and glial cells appear to contain VEGF. The VEGF receptor flt was induced in endothelial cells along with the progression of angiogenesis in infarct. The VEGF/flt system is thus considered to be involved in the healing process of brain infarct.
Editorial Comment
Expression Time Kinetics in Rat Brain Infarct
CNS Growth Factor Research LaboratoryDepartment of NeurologyMassachusetts General HospitalBoston, Mass
This article has been cited by other articles:
 |
|
 |
|
  E. P. Meyer, A. Ulmann-Schuler, M. Staufenbiel, and T. Krucker Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease PNAS, March 4, 2008; 105(9): 3587 - 3592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Jin, X. Wang, L. Xie, X. O. Mao, W. Zhu, Y. Wang, J. Shen, Y. Mao, S. Banwait, and D. A. Greenberg Evidence for stroke-induced neurogenesis in the human brain PNAS, August 29, 2006; 103(35): 13198 - 13202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kilic, U. Kilic, Y. Wang, C. L. Bassetti, H. H. Marti, and D. M. Hermann The phosphatidylinositol-3 kinase/Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia FASEB J, June 1, 2006; 20(8): 1185 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shimamura, N. Sato, S. Waguri, Y. Uchiyama, T. Hayashi, H. Iida, T. Nakamura, T. Ogihara, Y. Kaneda, and R. Morishita Gene Transfer of Hepatocyte Growth Factor Gene Improves Learning and Memory in the Chronic Stage of Cerebral Infarction Hypertension, April 1, 2006; 47(4): 742 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kimura, H. Nakase, R. Tamaki, and T. Sakaki Vascular Endothelial Growth Factor Antagonist Reduces Brain Edema Formation and Venous Infarction Stroke, June 1, 2005; 36(6): 1259 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Osuka, Y. Watanabe, N. Usuda, A. Nakazawa, M. Tokuda, and J. Yoshida Modification of Endothelial NO Synthase Through Protein Phosphorylation After Forebrain Cerebral Ischemia/Reperfusion Stroke, November 1, 2004; 35(11): 2582 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ferrara Vascular Endothelial Growth Factor: Basic Science and Clinical Progress Endocr. Rev., August 1, 2004; 25(4): 581 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Rosenstein, N. Mani, A. Khaibullina, and J. M. Krum Neurotrophic Effects of Vascular Endothelial Growth Factor on Organotypic Cortical Explants and Primary Cortical Neurons J. Neurosci., December 3, 2003; 23(35): 11036 - 11044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Jin, Y. Zhu, Y. Sun, X. O. Mao, L. Xie, and D. A. Greenberg Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo PNAS, September 3, 2002; 99(18): 11946 - 11950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pleasure, P. Bannerman, J. Ara, M. Scarlato, and T. Itoh Prospects for Vascular Endothelial Growth Factor Neurotherapeutics Arch Neurol, May 1, 2002; 59(5): 692 - 694. [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Lee, H. Avraham, S.-H. Lee, and S. Avraham Vascular Endothelial Growth Factor Modulates Neutrophil Transendothelial Migration via Up-regulation of Interleukin-8 in Human Brain Microvascular Endothelial Cells J. Biol. Chem., March 15, 2002; 277(12): 10445 - 10451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Becker, A. D. Verin, M. A. Booth, F. Liu, A. Birukova, and J. G. N. Garcia Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1500 - L1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. White, D. L. Livant, S. Markwart, and D. A. Arenberg Monocyte-Fibronectin Interactions, Via {alpha}5{beta}1 Integrin, Induce Expression of CXC Chemokine-Dependent Angiogenic Activity J. Immunol., November 1, 2001; 167(9): 5362 - 5366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wei, J. P. Erinjeri, C. M. Rovainen, and T. A. Woolsey Collateral Growth and Angiogenesis Around Cortical Stroke Stroke, September 1, 2001; 32(9): 2179 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Calzà, L. Giardino, A. Giuliani, L. Aloe, and R. Levi-Montalcini Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors PNAS, March 16, 2001; (2001) 51626998. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Beck, T. Acker, C. Wiessner, P. R. Allegrini, and K. H. Plate Expression of Angiopoietin-1, Angiopoietin-2, and Tie Receptors after Middle Cerebral Artery Occlusion in the Rat Am. J. Pathol., November 1, 2000; 157(5): 1473 - 1483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Kazi, W. S. Lee, E. Wagner, and P. M. Becker VEGF, fetal liver kinase-1, and permeability increase during unilateral lung ischemia Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L460 - L467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Jin, X. O. Mao, and D. A. Greenberg Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia PNAS, August 29, 2000; 97(18): 10242 - 10247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Slevin, J. Krupinski, A. Slowik, P. Kumar, A. Szczudlik, and J. Gaffney Serial Measurement of Vascular Endothelial Growth Factor and Transforming Growth Factor-{beta}1 in Serum of Patients With Acute Ischemic Stroke Stroke, August 1, 2000; 31(8): 1863 - 1870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Becker, A. Alcasabas, A. Y. Yu, G. L. Semenza, and T. E. Bunton Oxygen-Independent Upregulation of Vascular Endothelial Growth Factor and Vascular Barrier Dysfunction during Ventilated Pulmonary Ischemia in Isolated Ferret Lungs Am. J. Respir. Cell Mol. Biol., March 1, 2000; 22(3): 272 - 279. [Abstract] [Full Text]
|
|
|
|
|
|
H. J. H. Marti, M. Bernaudin, A. Bellail, H. Schoch, M. Euler, E. Petit, and W. Risau Hypoxia-Induced Vascular Endothelial Growth Factor Expression Precedes Neovascularization after Cerebral Ischemia Am. J. Pathol., March 1, 2000; 156(3): 965 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dammann and A. Leviton Brain Damage in Preterm Newborns: Might Enhancement of Developmentally Regulated Endogenous Protection Open a Door for Prevention? Pediatrics, September 1, 1999; 104(3): 541 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fischer, M. Clauss, M. Wiesnet, D. Renz, W. Schaper, and G. F. Karliczek Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO Am J Physiol Cell Physiol, April 1, 1999; 276(4): C812 - C820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N.-T. Kuo, D. Benhayon, R. J. Przybylski, R. J. Martin, and J. C. LaManna Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain J Appl Physiol, January 1, 1999; 86(1): 260 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Marti and W. Risau Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors PNAS, December 22, 1998; 95(26): 15809 - 15814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Cheng, M. Nagane, H.-J. S. Huang, and W. K. Cavenee Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189 PNAS, October 28, 1997; 94(22): 12081 - 12087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi, K. Abe, H. Suzuki, and Y. Itoyama Rapid Induction of Vascular Endothelial Growth Factor Gene Expression After Transient Middle Cerebral Artery Occlusion in Rats Stroke, October 1, 1997; 28(10): 2039 - 2044. [Abstract] [Full Text]
|
|
|
|
|
|
L. Calza, L. Giardino, A. Giuliani, L. Aloe, and R. Levi-Montalcini Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors PNAS, March 27, 2001; 98(7): 4160 - 4165. [Abstract] [Full Text] [PDF]
|
|