RADIATION-INDUCED CHANGES IN THE PROFILE OF SPINAL-CORD SEROTONIN, PROSTAGLANDIN SYNTHESIS, AND VASCULAR-PERMEABILITY

Purpose: To investigate the profile of biochemical and physiological c hanges induced in the rat spinal cord by radiation, over a period of 8 months. Methods and Materials: The thoraco-lumbar spinal cords of Fis her rats were irradiated to a dose of 15 Gy. The rats were then follow ed and killed at various times afterward. Serotonin (5-HT) and its maj or metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as w ell as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. Results: N one of the rats developed neurologic dysfunction, and histologic exami nation revealed only occasional gliosis in the ventral white matter at 240 days after irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thora cic and cervical segments (p < 0.01) and age-matched controls (p < 0.0 3). The calculated utilization ratio of serotonin (5-HIAA/S-HT) remain ed unchanged. Immediately after radiation (at 3 and 24 h) an abrupt bu t brief increase in the synthesis of prostaglandin-E(2) (PGE(2)), thro mboxane (TXB(2)), and prostacyclin [6 keto-PGF1 alpha (6KPGF)] was not ed, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglan dins. Thereafter, at 28, 56, 120, and 240 days, escalated production o f thromboxane followed, while prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radia tion the calculated TXB(2)/6KPGF ratio remained balanced, regardless o f the observed abrupt early fluctuations in their rate of synthesis. L ater, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was obser ved which returned to normal by 3 days. Normal permeability was mainta ined at 14 and 28 days, but at 120 and 240 days a persistent and signi ficant increase of 98% and 73% respectively above control level was no ted. Conclusions: Radiation induces severe impairment in microvessel f unction even in the histologically unaffected spinal cord, and alters the secretory phenotype of various cell systems in the central nervous system.