title: The roles of platelet-derived growth factors and their receptors in brain radiation necrosis.
abstract: BACKGROUND
  Brain radiation necrosis (RN) occurring after radiotherapy is a serious complication. We and others have performed several treatments for RN, using anticoagulants, corticosteroids, surgical resection and bevacizumab. However, the mechanisms underlying RN have not yet been completely elucidated. For more than a decade, platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have been extensively studied in many biological processes. These proteins influence a wide range of biological responses and participate in many normal and pathological conditions. In this study, we demonstrated that PDGF isoforms (PDGF-A, B, C, and D) and PDGFRs (PDGFR-α and β) are involved in the pathogenesis of human brain RN. We speculated on their roles, with a focus on their potential involvement in angiogenesis and inflammation in RN.
  
  
  METHODS
  Seven surgical specimens of RN, obtained from 2006 to 2013 at our department, were subjected to histopathological analyses and stained with hematoxylin and eosin. We qualitatively analyzed the protein expression of each isoform of PDGF by immunohistochemistry. We also examined their expression with double immunofluorescence.
  
  
  RESULTS
  All PDGFs were expressed in macrophages, microglia, and endothelial cells in the boundary of the core of RN, namely, the perinecrotic area (PN), as well as in undamaged brain tissue (UB). PDGF-C, D and PDGFR-α were also expressed in reactive astrocytes in PN. PDGFs and PDGFR-α were scarcely detected in UB, but PDGFR-β was specifically expressed in endothelial cells not only in PN but also in UB.
  
  
  CONCLUSIONS
  PDGFs/PDGFRs play critical roles in angiogenesis and possibly in inflammation, and they contribute to the pathogenesis of RN, irrespective of the original tumor pathology and applied radiation modality. Treatments for the inhibition of PDGF-C, PDGF-D, and PDGFR-α may provide new approaches for the treatment of RN induced by common radiation therapies.
authors: Tomo
authors: T
authors: Miyata
authors: Taichiro
authors: T
authors: Toho
authors: Naosuke
authors: N
authors: Nonoguchi
authors: Motomasa
authors: M
authors: Furuse
authors: Hiroko
authors: H
authors: Kuwabara
authors: Erina
authors: E
authors: Yoritsune
authors: Shinji
authors: S
authors: Kawabata
authors: Toshihiko
authors: T
authors: Kuroiwa
authors: Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. neu070@poh.osaka-med.ac.jp.
authors: Shin-Ichi
authors: S
authors: Miyatake
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000209:etiology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011832:Radiation Injuries; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor