Endothelial apoptosis initiates acute blood-brain barrier disruption after ionizing radiation Journal Article
| Authors: | Li, Y. Q.; Chen, P.; Haimovitz-Friedman, A.; Reilly, R. M.; Wong, C. S. |
| Article Title: | Endothelial apoptosis initiates acute blood-brain barrier disruption after ionizing radiation |
| Abstract: | Acute disruption of blood-brain barrier (BBB) is well recognized after radiation therapy to the central nervous system (CNS). We assessed the genetic regulation of acute BBB disruption and its relationship to vascular endothelial cell death in the CNS after irradiation. Adult rats were given graded single doses of X-ray to the cervical spinal cord. At different time intervals after irradiation, the irradiated spinal cord was processed for histological and immunohistochemical analysis. Disruption of blood-spinal cord barrier was assessed using albumin immunohistochemistry, i.v. injection of Evans blue dye, and 99mTc-diethylenetriamine pentaacetic acid. In the rat spinal cord, there was a dose-dependent apoptotic response during the first 24 h after irradiation, and apoptotic cells consisted of both endothelial and glial cells, as described previously (1, 2). A dose-dependent reduction in endothelial cell density was observed at 24 h after irradiation. This was associated with a similar dose-dependent disruption in blood-spinal cord barrier as demonstrated by albumin immunohistochemistry. Radiation-induced apoptosis in endothelial cells has been shown to be dependent on the acid sphingomyelinase (ASMase) pathway. After a single 50-Gy dose to the cervical spinal cord of ASMase +/+ mice, there was a 47.7% reduction in endothelial cell density at 24 h compared with nonirradiated controls. No decrease in endothelial cell density was observed in irradiated ASMase -/- mice. In the irradiated spinal cord of ASMase +/+ mice, there was evidence of albumin immunoreactivity and Evans blue dye staining around microvessels, and 99mTc-diethylenetriamine pentaacetic acid uptake increased at 24 h. Nonirradiated controls and the irradiated spinal cord of ASMase -/- mice demonstrated no evidence of leakage. We conclude that apoptosis of endothelial cells initiates acute BBB disruption in the CNS after irradiation and that acute BBB disruption after irradiation is mediated by the ASMase pathway. |
| Keywords: | immunohistochemistry; controlled study; histopathology; dose response; nonhuman; cancer radiotherapy; radiation dose; animal cell; animals; mice; apoptosis; animal experiment; animal model; mice, inbred c57bl; central nervous system; dose-response relationship, radiation; mice, transgenic; endothelium cell; albumin; vascular endothelium; endothelium, vascular; spinal cord; rat; blood brain barrier; blood-brain barrier; ionizing radiation; glia cell; rats; cell density; sphingomyelin phosphodiesterase; rats, inbred f344; cervical spine; pentetate technetium tc 99m; evans blue; female; priority journal; article |
| Journal Title: | Cancer Research |
| Volume: | 63 |
| Issue: | 18 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2003-09-15 |
| Start Page: | 5950 |
| End Page: | 5956 |
| Language: | English |
| PUBMED: | 14522921 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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