| RRC ID |
2775
|
| 著者 |
Kumai Y, Ooboshi H, Ibayashi S, Ishikawa E, Sugimori H, Kamouchi M, Kitazono T, Egashira K, Iida M.
|
| タイトル |
Postischemic gene transfer of soluble Flt-1 protects against brain ischemia with marked attenuation of blood-brain barrier permeability.
|
| ジャーナル |
J Cereb Blood Flow Metab
|
| Abstract |
Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. Our goal in this study was to explore protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vector encoding sFlt-1 or beta-galactosidase as control was injected into the lateral ventricle 90 mins after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released to the cerebrospinal fluid from the ventricular wall and significantly increased 6 h, 1 and 7 days after sFlt-1 transfection. One day after brain ischemia, sFlt-1 gene transfer significantly reduced infarct volume (by 35%), brain edema (by 35%), and blood-brain barrier permeability (Evans blue extravasation; by 69%) with diminished phosphorylation of focal adhesion kinase (FAKtyr397 and FAKtyr861) in the ischemic vessels. Seven days after ischemia, sFlt-1 gene transfer also significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%), although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be useful for brain infarction.
|
| 巻・号 |
27(6)
|
| ページ |
1152-60
|
| 公開日 |
2007-6-1
|
| DOI |
10.1038/sj.jcbfm.9600420
|
| PII |
9600420
|
| PMID |
17077813
|
| MeSH |
Animals
Blood-Brain Barrier / metabolism*
Brain Ischemia / prevention & control
Brain Ischemia / therapy*
Chemotaxis
Genetic Therapy / methods*
Male
Monocytes / physiology
Neovascularization, Physiologic / drug effects
Permeability
Pharmacokinetics
Rats
Rats, Inbred SHR
Transduction, Genetic / methods
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Vascular Endothelial Growth Factor Receptor-1 / administration & dosage*
|
| IF |
5.681
|
| 引用数 |
30
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
HEMATOLOGY
NEUROSCIENCES
|
| リソース情報 |
| ラット |
SHR/Kyo(strainID=9) |
