Korean J Cerebrovasc Surg.  2009 Mar;11(1):12-18.

Radiation Induced Senescence-like Changes of Endothelial Cells and Blood-brain Barrier Disruption

Affiliations
  • 1Department of Neurosurgery, East-West Neo Medical Center of Kyung Hee University, Seoul, Korea.
  • 2Department of Neurosurgery, Bun-dang Seoul National University Hospital, Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. wanoh@snu.ac.kr

Abstract


OBJECTIVES
This study was performed to evaluate the relationship between radiation induced senescence-like changes of endothelial cells and blood-brain barrier disruption. MATERIALS AND METHODS: Radiation of 15 Gy was applied to a monolayer culture of bovine aortic endothelial cells (BAEC). The morphological changes were observed over 19 weeks. An artificial blood-brain barrier (BBB) model was constructed using the Transwell(R) and co-culture of the BAEC with C6 glioma cells. After treatment with the same dose of radiation, changes in the BBB were observed by measurement of the trans-endothelial electrical resistance (TEER). RESULTS: Senescence-like changes of the endothelial cells appeared 1 week after irradiation; it was most prominent during the third week and replacement by normal endothelial cells was noted from the seventh week. The recovered normal endothelial monolayer was maintained until the 19th week. Senescence-like endothelial cells showed positive staining with senescence-associated beta-galactosidase (SA-beta-gal). In the Transwell(R), the TEER began to decrease 1 week after irradiation, and the decreased resistance reached its peak 18 days after irradiation, and then began to recover to some degree. CONCLUSION : After application of radiation (15 Gy), senescence-like changes of the endothelial cells were observed in the monolayer culture. These findings demonstrated good correlation with the disruption of blood-brain barrier in an in-vitro model of the BBB.

Keyword

Senescence; Endothelial cells; Radiation; Blood-brain barrier

MeSH Terms

Aging
beta-Galactosidase
Blood-Brain Barrier
Coculture Techniques
Electric Impedance
Endothelial Cells
Glioma
beta-Galactosidase
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