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Delayed brain radiation necrosis: pathological review and new molecular targets for treatment

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Abstract

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell–cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

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Acknowledgments

This work was partly supported by a Grant-in-Aid for Scientific Research (C) (26462222) given to M.F. from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

  1. Department of Neurosurgery, Osaka Medical College, 2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan

    Motomasa Furuse, Naosuke Nonoguchi, Shinji Kawabata, Shin-Ichi Miyatake & Toshihiko Kuroiwa

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  1. Motomasa Furuse
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  2. Naosuke Nonoguchi
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  3. Shinji Kawabata
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  4. Shin-Ichi Miyatake
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  5. Toshihiko Kuroiwa
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Correspondence to Motomasa Furuse.

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Furuse, M., Nonoguchi, N., Kawabata, S. et al. Delayed brain radiation necrosis: pathological review and new molecular targets for treatment. Med Mol Morphol 48, 183–190 (2015). https://doi.org/10.1007/s00795-015-0123-2

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