Regional, cellular, and subcellular distribution of [ 3H]dexamethasone in rat brain edema

Abstract

The regional, cellular, and subcellular distribution of [ 3H]dexamethasone in brain edema of rats was studied. Edema was induced either by occlusion of the right carotid artery or by a cold lesion of the right temporal lobe. [ 3H]dexamethasone (0.3 mCi) was injected intravenously. After 30 minutes (unless otherwise stated) the brains and other desired organs were removed. In the control animals, 51% of the total [ 3H]dexamethasone activity was found in the cerebral hemispheres (27% in the right, 24% in the left), 24% in the cerebellum, and 24% in the brainstem. Time-course studies revealed a rapid decline of [ 3H]dexamethasone content in all regions of the brain. After 48 hours of ligation of the right carotid artery, 80% of the [ 3H]dexamethasone could be found in the cerebral hemispheres (48% in the right, 32% in the left), 10% in the cerebellum, and 9% in the brainstem. In the series in which cold lesions were induced, 74% of the [ 3H]dexamethasone was recovered in the cerebral hemispheres (40% in the right (lesion), 34% in the left (control)). Before the trauma, 75% of the dexamethasone was found in astrocytes and 25% in neurons; after the trauma, 48% was bound to astrocytes and 42% to neurons. At the subcellular level, accumulation took place in the microsomal, lysosomal, and cytoplasmic fractions of the damaged cells. These data demonstrate an increased uptake of dexamethasone into ischemic damaged brain tissue and into neurons, microsomes, and lysosomes.