Oxygen tension regulates the maturation of the blood-brain barrier.
The oxygen tension during the development of vascular systems influences vascular vessel formation through regulating angiogenesis. We studied the effect of hypoxia/reoxygenation (H/R) to explain its role in concert with astrocytes involvement in the development of the blood-brain barrier (BBB). On the basis of the fact that the disappearance of hypoxic regions and the decreased expression of vascular endothelial growth factor (VEGF) were observed by immunohistochemistry in a development-dependent manner in rat cerebral cortex, we examined the effects of astrocytes on the BBB-like properties of ECV304 cells by exposing astrocytes to H/R. Conditioned medium of reoxygenated astrocytes inhibited [(3)H]thymidine incorporation and tube formation of ECV 304 cells. When astrocytes were exposed to reoxygenation, the expression of VEGF was reduced, whereas the expression of angiopoietin-1 and thrombospondin-1 was enhanced. Moreover, [(3)H]sucrose permeability assay revealed that astrocytes enhance the barrier function of ECV 304 cells in coculture model within 5 h of reoxygenation. Correspondingly, the occludin expression of ECV 304 cells was slightly increased by the conditioned medium of reoxygenated astrocytes. In conclusion, our study suggests that reoxygenation of astrocytes may act as a significant driving force for the maturation of the BBB during brain development through oxygen-regulated gene(s).
Song
Hyun Seok
HS
Department of Molecular Biology, Pusan National University, Pusan, Korea.
Son
Myung Jin
MJ
Lee
You Mie
YM
Kim
Woo Jean
WJ
Lee
Sae-Won
SW
Kim
Chul Woo
CW
Kim
Kyu-Won
KW
D042683:Angiopoietin-1; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D006801:Humans; D000860:Hypoxia; D015151:Immunoblotting; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D062793:Occludin; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000378:metabolism; D019700:Thrombospondin 1 / Q000096:biosynthesis; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013395:Sucrose; C012439:methylthymidine; D010100:Oxygen; D013936:Thymidine