: PurposeThe aim of this study was to assess changes in oligodendrocytes (OL), myelin gene expression, and their relationships with late demyelination after irradiation.: Methods and materialsAdult rats were given single doses of 8 or 22 Gy to the cervical spinal cord. Immunohistochemistry for APC or GST-π was used to identify OL. Changes in myelin gene expression were assessed using RT-PCR for proteolipid protein (PLP). Luxol fast blue staining was used to assess demyelination. CNP-βgeo transgenic mice were used to confirm some of the results of the rat model. Cells of the oligodendroglial lineage in these animals express β-galactosidase (β-gal).: ResultsEarly apoptosis of APC, GST-π, and β-galactosidase positive cells was observed in the spinal cord of rats and CNP-βgeo mice. At 24 h after 22 Gy, there was a significant decrease in OL density. Cell density continued to decline thereafter after both 8 and 22 Gy, and a reduction in PLP expression was observed at 4–5 weeks. A further decrease in PLP expression was seen beginning at 18 weeks after 22 Gy only. Demyelination was observed at 19 weeks after 22 Gy.: ConclusionsApoptosis of OL and changes in OL density and PLP gene expression were observed early after both 8 and 22 Gy. This suggests that these early changes are unlikely to be directly related to the late demyelination observed. [Copyright &y& Elsevier]