Rodent model of chemoradiotherapy-induced white matter necrosis.
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.
Taylor
E M
EM
Department of Medicine, Jennifer Sacco International Research Laboratories, Children's Hospital, Seattle, WA.
Geyer
J R
JR
Milstein
J M
JM
Shaw
C M
CM
Geraci
J P
JP
Wootton
P
P
Hubbard
B A
BA
Bleyer
W A
WA
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
D008727:Methotrexate