Myelin-associated changes in mouse brain following irradiation

Abstract

The goals of this study were to quantify myelin-associated changes in the brain following single doses of radiation and to determine their relationship to the dose limits that this tissue can tolerate. Mice developed a transient loss of balance 1 month after 60 Gy doses 250 kV p X-rays to the brain and 3–4 months after 30–45 Gy radiation, but not after lower doses. The symptoms were transient and lasted ∼ 1 month. The ED 50 300 for radiation-induced brain death, which occurred largely between 200 and 240 days, was 32.4 Gy (29.1, 35.5 Gy, 95% confidence limit of mean). At the time that animals developed neurological symptoms, 3–4 months after irradiation with doses of 30–45 Gy, biochemical assays of myelin-associated proteins showed decreases in 2′,3′-cyclic nucleotide phosphohydrolase (CNPase) and myelin basic protein (MBP) levels that were not seen with lower radiation doses. By 120–180 days, further dose-dependent decreases in both CNPase and MBP levels were found after 20–45 Gy irradiation that preceded and correlated with death. The correlation of the decrease in CNPase and MBP levels with the incidence of transient neurological malfunction and animal death, together with histological evidence, suggests that demyelination is responsible for these phenomena.