VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: both effects decreased by Ang-1 - Archive ouverte HAL Access content directly
Journal Articles Journal of Cerebral Blood Flow and Metabolism Year : 2005

VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: both effects decreased by Ang-1

(1) , , (2) , (3) , , (3) , (4) , (4) , (4) , (4) , (4)
1
2
3
4

Abstract

After cerebral ischemia, angiogenesis, by supplying for the deficient perfusion, may be a beneficial process for limiting neuronal death and promoting tissue repair. In this study, we showed that the combination of Ang-1 and vascular endothelial growth factor (VEGF) provides a more adapted therapeutic strategy than the use of VEGF alone. Indeed, we showed on a focal ischemia model that an early administration of VEGF exacerbates ischemic damage, because of its effects on blood-brain barrier (BBB) permeability. In contrast, a coapplication of Ang-1 and VEGF leads to a significant reduction of the ischemic and edema volumes by 50% and 42%, respectively, in comparison with VEGF-treated mice. We proposed that Ang-1 blocks the BBB permeability effect of VEGF in association with a modulation of matrix metalloproteinase (MMP) activity. Indeed, we showed on both ischemic in vivo and BBB in vitro models that VEGF enhances BBB damage and MMP-9 activity and that Ang-1 counteracts both effects. However, we also showed a synergic angiogenic effect of Ang-1 and VEGF in the brain. Taken together, these results allow to propose that, in cerebral ischemia, the combination of Ang-1 and VEGF could be used early to promote the formation of mature neovessels without inducing side effects on BBB permeability.
Not file

Dates and versions

hal-00542804 , version 1 (03-12-2010)

Identifiers

  • HAL Id : hal-00542804 , version 1

Cite

Samuel Valable, Joan Montaner, Anita Bellail, Vincent Berezowski, Julien Brillault, et al.. VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: both effects decreased by Ang-1. Journal of Cerebral Blood Flow and Metabolism, 2005, p. 1-14. ⟨hal-00542804⟩
268 View
0 Download

Share

Gmail Facebook Twitter LinkedIn More