期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 22, 期 4, 页码 379-392出版社
SAGE PUBLICATIONS INC
DOI: 10.1097/00004647-200204000-00002
关键词
VEGF; angiopoietins; BBB; angiogenesis
资金
- NHLBI NIH HHS [R01HL 64766] Funding Source: Medline
- NINDS NIH HHS [R0138292NS, P01 NS23393, R01 NS33627] Funding Source: Medline
In an effort to elucidate the molecular mechanisms underlying cerebral vascular alteration after stroke, the authors measured the spatial and temporal profiles of blood-brain barrier (131313) leakage, angiogenesis, vascular endothelial growth factor (VEGF), associated receptors, and angiopoietins and receptors after embolic stroke in the rat. Two to four hours after onset of ischemia, VEGF mRNA increased, whereas angiopoietin 1 (Ang 1) mRNA decreased. Three-dimensional immunofluorescent analysis revealed spatial coincidence between increases of VEGF immunoreactivity and 131313 leakage in the ischemic core. Two to 28 days after the onset of stroke, increased expression of VEGF/VEGF receptors and Ang/Tie2 was detected at the boundary of the ischemic lesion. Concurrently, enlarged and thin-walled vessels were detected at the boundary of the ischemic lesion, and these vessels developed into smaller vessels via sprouting and intussusception. Three-dimensional quantitative analysis of cerebral vessels at the boundary zone 14 days after ischemia revealed a significant (P < 0.05) increase in numbers of vessels (n = 365) compared with numbers (n = 66) in the homologous tissue of the contralateral hemisphere. Furthermore, capillaries in the penumbra had a significantly smaller diameter (4.8 +/- 2.0 mum) than capillaries (5.4 +/- 1.5 mum) in the homologous regions of the contralateral hemisphere. Together, these data suggest that acute alteration of VEGF and Ang I in the ischemic core may mediate 131313 leakage, whereas upregulation of VEGF/VEGF receptors and Ang/Tie2 at the boundary zone may regulate neovascularization in ischemic brain.
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