Dose-response relation for dexamethasone in cold lesion-induced brain edema in rats

A dose-response relation was established for the antiedematous effect of dexamethasone in the rat brain, using the model of cold lesion-induced brain edema. Four doses corresponding to a human dose of 20 mg, 100 mg, 500 mg, and 2,500 mg dexamethasone (Fortecortin, E. Merck, Darmstadt, Germany) resulted in a highly significant edema reduction by 25%, 30%, and 50%, respectively, although the megadose of 2,500 mg showed less effect, only 30% reduction. Reproducible conditions with regard to animal material and sophisticated method used, exact analysis, manufacture and stability of the test substance dexamethasone, and scatter-reducing techniques and calculation procedures were the prerequisites for the clear result of the study. These results with the optimal dose of 500 mg dexamethasone obtained confirm recent therapy concepts in antiedematous therapy with ultra-high doses of dexamethasone in head injury. Carefully designed clinical studies on the subject of head injury and glucocorticoids may therefore be considered as extremely promising.