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

방사선 조사로 유도된 내피세포의 유사 - 노화 현상과 혈뇌장벽 장애

  • Bang, Jae-Seung (Department of Neurosurgery, East-West Neo Medical Center of Kyung Hee University) ;
  • Kwon, O-Ki (Department of Neurosurgery, Bun-dang Seoul National University Hospital, Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Oh, Chang-Wan (Department of Neurosurgery, Bun-dang Seoul National University Hospital, Department of Neurosurgery, Seoul National University College of Medicine)
  • 방재승 (경희대학교 동서신의학병원 신경외과) ;
  • 권오기 (서울대학교의과대학 신경외과학교실 분당서울대학교병원 신경외과) ;
  • 오창완 (서울대학교의과대학 신경외과학교실 분당서울대학교병원 신경외과)
  • Published : 2009.03.30

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 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, 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.

Keywords