The pathophysiology of the cellular basis of radiation induced demyelination and white matter necrosis of the Central Nervous System (CNS) is poorly understood. There have been no previous studies that have shown the effect of irradiation on glia-derived nexin. In this study, rats were given cervical spinal cord irradiation, and glial derived nexin or protease nexin I (GDN/PNI) was measured on days 2, 7, 30, 60, 120, 130, and 145 after irradiation. The level of GDN/PNI significantly decreased after irradiation compared to levels in control spinal cord, and there was no detectable levels of GDN/PNI by the time paralysis developed. This study adds considerable weight to the proposal that GDN/PNI has an important role in the pathogenesis of CNS radiation damage.