title: Effects of irradiation on brain vasculature using an in situ tumor model.
abstract: OBJECTIVE
  Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model.
  
  
  METHODS
  Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells.
  
  
  RESULTS
  The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation.
  
  
  CONCLUSIONS
  We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.
authors.affiliation: School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Zawaski
authors.forename: M Waleed
authors.initials: MW
authors.lastname: Gaber
authors.forename: Omaima M
authors.initials: OM
authors.lastname: Sabek
authors.forename: Christy M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Duntsch
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
mesh_terms: D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000502:physiology / Q000528:radiation effects*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*; D002448:Cell Adhesion / Q000528:radiation effects; D004396:Coloring Agents / Q000493:pharmacokinetics; D019583:Dose Fractionation, Radiation; D004730:Endothelium, Vascular / Q000502:physiology / Q000528:radiation effects*; D005910:Glioma / Q000098:blood supply / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*; D005911:Gliosis / Q000473:pathology; D036904:Leukocyte Rolling / Q000502:physiology / Q000528:radiation effects; D007962:Leukocytes / Q000502:physiology / Q000528:radiation effects; D008297:Male; D023421:Models, Animal; D010539:Permeability / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D047368:Tumor Burden / Q000528:radiation effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D004396:Coloring Agents; D042461:Vascular Endothelial Growth Factor A