J Korean Neurol Assoc.  2002 Sep;20(5):530-536.

Delayed Up-regulation of Vascular Endothelial Growth Factor and flk-1 after Global Cerebral Ischemia in Mongolian Gerbil: Possible roles in neuroangiogenesis?

• Park KI
• Chu K
• Kim DE
• Park HK
• Ahn SS
• Park SH
• Kim MH
• Roh JK

Abstract

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a potent mediator of vascular permeability. Flk-1, one of the receptors for VEGF, is important in vascular development. Increased expression of VEGF is related with reactive astrogliosis, which stimulates the proliferation of neural progenitor cells. VEGF expression increases in the acute phase of cerebral ischemia, however the expression of VEGF together with flk-1 in subacute stage is still unknown. This study is done to demonstrate the spatial/cellular patterns of expression for VEGF/flk-1 up to subacute stages and to find out the role of VEGF in ischemia.
METHODS
Transient global ischemia was induced by a 10 min-occlusion/reperfusion of the bilateral carotid arteries in the Mongolian gerbil. Immunohistochemistry and western blot were performed to ensure the expression of VEGF and flk-1 on the day 1, 3, 7, 14, and 28.
RESULTS
Both VEGF and flk-1 initially increased at day1, and decreased at day 3. Thereafter, VEGF gradually increased again to the initial level at day 7 and to the peak level after day 14. Flk-1 showed a peak expression at day 14, and then decreased at day 28. Immunohistochemical staining for VEGF showed immunoreactivity mainly on the cytoplasm of neurons and endothelium in cortex and hippocampus at day 1, and neuron, endothelium, and glial cell from day 14 to 28. The distribution and chronological patterns of flk-1 expression were similar to that of VEGF expression.
CONCLUSIONS
We suggest that global cerebral ischemia can induce a delayed up-regulation of VEGF and flk-1, which may be associated with neuroangiogenesis and repair process.

Keyword

Vascular endothelial growth factor; Fetal liver kinase-1; Delayed up-regulation; Neuroangiogenesis; Globalischemia

MeSH Terms

Blotting, Western
Brain Ischemia*
Capillary Permeability
Carotid Arteries
Cytoplasm
Endothelium
Gerbillinae*
Hippocampus
Immunohistochemistry
Ischemia
Neuroglia
Neurons
Stem Cells
Up-Regulation*
Vascular Endothelial Growth Factor A*
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2