PROGRESSIVE PERTURBATIONS IN CEREBRAL ENERGY-METABOLISM AFTER EXPERIMENTAL WHOLE-BRAIN RADIATION IN THE THERAPEUTIC RANGE

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation have not been fully elucidated in the literature. The authors employed the [C-14]-2-deoxy-D-glucose autoradiography method to investigate the effect of whole-brain x-irradiation on local cerebral glucose utilization in the rat brain. The animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week for a total dose of 4000 cGy), and the effects of this regimen were assessed at 2 weeks and 3 months postirradiation. In rats evaluated 2 weeks after treatment, statistically significant decreases in cerebral metabolic activity were found in 13 of the 27 regions studied, compared to control animals. In rats studied 3 months after treatment, additional metabolic suppression and statistically significant decreases in cerebral metabolic activity were found in 11 of the 27 regions, compared to rats studied 2 weeks after treatment. A weighted-average rate for the brain as a whole was approximately 15% and approximately 25% below that of control animals 2 weeks and 3 months after exposure, respectively. Although the difference in species is significant enough so that direct extrapolation to humans may not be appropriate, the data reported here may have potential clinical implications for the evaluation of the risk-benefit ratio for radiotherapy. This model can be used reproducibly for further investigations, including evaluation of therapies that may reduce irradiation-induced brain injury.