title: Rodent model of chemoradiotherapy-induced white matter necrosis.
abstract: This report describes a laboratory model that permits study of the radiochemotherapy interactions in the CNS. Rats are stereotaxically implanted with a cerebroventricular cannula attached to an osmotic minipump, which slowly infuses a chemotherapeutic agent into CSF for up to 14 days. The cervical cord is irradiated, and forelimb paralysis develops 4-6 months later at an effective dose for paresis in 50% of the animals; the doses with radiotherapy alone are 2,125 cGy for a single fraction and 2,950 cGy for split fractions. Investigations with the model indicate that mature CNS tissue is not sensitized to either single-fraction or split-dose irradiation with either simultaneous or post-radiation exposure to high concentrations of methotrexate.
authors.affiliation: Department of Medicine, Jennifer Sacco International Research Laboratories, Children's Hospital, Seattle, WA.
authors.forename: E M
authors.initials: EM
authors.lastname: Taylor
authors.forename: J R
authors.initials: JR
authors.lastname: Geyer
authors.forename: J M
authors.initials: JM
authors.lastname: Milstein
authors.forename: C M
authors.initials: CM
authors.lastname: Shaw
authors.forename: J P
authors.initials: JP
authors.lastname: Geraci
authors.forename: P
authors.initials: P
authors.lastname: Wootton
authors.forename: B A
authors.initials: BA
authors.lastname: Hubbard
authors.forename: W A
authors.initials: WA
authors.lastname: Bleyer
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008727:Methotrexate / Q000097:blood / Q000633:toxicity*; D009336:Necrosis; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008727:Methotrexate