title: Delayed brain radiation necrosis: pathological review and new   molecular targets for treatment.
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.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Furuse
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawabata
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Miyatake
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016207:Cytokines / Q000378:metabolism; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D009336:Necrosis / Q000209:etiology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology / Q000528:radiation effects; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A