A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone

Abstract

In order to identify the effects of x-irradiation on spinal cord histology and capillary permeability, we irradiated the upper thoracic spinal cord of adult rats with 3500 cGy to a single lateral field. After 165 +/- 14 (SD) days the rats became paraplegic over 4 to 8 days. Quantitative autoradiography using 14C-amino-isobutyric acid demonstrated a biphasic curve of regional capillary permeability changes (K1). K1 first increased 70 to 85% in all regions of the cord at 30 days, then normalized at 60 days. From 60-151 +/- 8 days in asymptomatic animals there was an apparently exponential increase of K1 in all spinal cord regions progressing at varying rates among regions, most rapidly in the posterior columns and least rapidly in grey matter. K1 continued to rise when the animals became paraplegic. Morphologically, the asymptomatic period was characterized by myelin pallor and vacuolation evident at 30 days, maximal at 60 days, without progression until 151 +/- 8 days when microscopic foci of necrosis appeared in the posterior columns of some clinically normal ('preparetic') animals. The paretic period was characterized by extensive posterior and lateral column necrosis with preservation of grey matter. High dose dexamethasone or indomethacin had no preventative effect when administered just prior to irradiation. Dexamethasone transiently improved motor strength in symptomatic rats and reduced K1 in nonnecrotic portions of the cord. This study suggests that, after a transient peak of 'early delayed' changes in regional capillary permeability, there is progressive damage to the endothelium that may play a primary role in delayed radionecrosis.