VEGF and flt. Expression time kinetics in rat brain infarct.
OBJECTIVE
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.
Kovács
Z
Z
Department of Neurosurgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Ikezaki
K
K
Samoto
K
K
Inamura
T
T
Fukui
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor