Changes in myelin basic protein and demyelination in the rat brain within 3 months of single 2-, 10-, or 30-Gy whole-brain radiation treatments

Abstract

The aim of this study was to determine the relation between changes in myelin basic protein (MBP) levels during the acute and subacute phases of central nervous system injury following whole-brain radiation and delayed demyelination in the radiation-injured brain tissue. Adult Sprague-Dawley rats were treated with single fractions of 2, 10, or 30 Gy of whole-brain radiation. The authors measured MBP gene expression and protein levels in the brain tissue by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay at 1 week and 1-3 months following irradiation to monitor myelin changes in the brain. Demyelination was determined with Luxol fast blue myelin staining and routine histopathological and electron microscopy examination of injured brain tissue. The changes in MBP levels in the different animal groups at specific time points were correlated with demyelination in corresponding dose groups. At 1 month after applying the 10 and 30 Gy of radiation, MBP mRNA expression showed a transient but significant decrease, followed by recovery to baseline levels at 3 months after treatment. The MBP levels were decreased by only 70-75% at 1 month after 10 and 30 Gy of radiation. At 2-3 months after applying the higher dose of 30 Gy, however, the MBP levels continued to decline, and typical demyelination changes were observed with myelin staining and ultrastructural examination. The authors' results suggest that the early radiation-induced MBP changes between 1 and 3 months after single treatments of 10 and 30 Gy of radiation to the whole brain are indicative of permanent injury shown as demyelination of irradiated brain tissue.