title: Effects of Targeted Proton Radiation on Spinal Cord in a Porcine Model: A Pilot Study.
abstract: OBJECTIVE
  To determine whether proton radiation can be used to treat chronic intractable pain. The focus of this study was on the biological effects of spinal cord irradiation.
  
  
  METHODS
  Proton radiation (0-25 Gy, single fraction) was applied to the spinal cord within L3-L5 of Yucatan mini-pigs (n=20). Skin reaction, body mass and behavior were monitored. At euthanasia, blood and spinal cord were analyzed.
  
  
  RESULTS
  Skin morbidity was mild and overall health for the 5-20 Gy-treated groups was good based on behavior and weight gain up to 8.5-9 months post-exposure. The 25 Gy-treated animals developed hind limb weakness at 2.5-3 months and were euthanized. Radiation had a significant effect on white blood cell count (p<0.05), with the 25 Gy-treated mini-pigs having the highest number of all three major leukocyte populations. A few differences were also noted for erythrocyte parameters, but the blood chemistry panel was normal. Apoptosis in the targeted portion of the spinal cord was elevated in the 20- and 25 Gy-treated groups versus 0 Gy (p<0.05) based on the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. There was a trend (p<0.1) for a radiation effect on glial fibrillary acidic protein expression, with the highest value being found after 25 Gy. Histology showed no difference between 0 versus 25 Gy.
  
  
  CONCLUSIONS
  The data demonstrated that a small segment of the spinal cord can be readily targeted using proton radiation; doses ranging from 5-20 Gy were well-tolerated in an animal model with radiosensitivity similar to humans. Future studies with a pain model should use ≤15 Gy.
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Mao
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.affiliation: Department of Human Anatomy & Pathology, Loma Linda University School of Medicine and Medical Center, Loma Linda, CA, U.S.A.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cao
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A. dgridley@llu.edu.
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D059350:Chronic Pain / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007958:Leukocyte Count; D010148:Intractable Pain / Q000473:pathology / Q000532:radiotherapy*; D010865:Pilot Projects; D061766:Proton Therapy; D013116:Spinal Cord / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000532:radiotherapy*; D013552:Swine; D013556:Swine, Miniature; D011522:Protons
chemical_list: D011522:Protons
keywords: Protons; apoptosis; astrogliosis; inflammation; mini-pig; pain; radiation