EFFECT OF STEROIDS ON EDEMA AND SODIUM UPTAKE OF THE BRAIN DURING FOCAL ISCHEMIA IN RATS

Steroids reduce permeability of the blood-brain barrier and inhibit active sodium transport by brain capillaries in vitro. Since the rate of edema formation during the early stages of ischemia is related to the rate of sodium transport from blood to brain, this study was designed to determine whether steroids reduce ischemic edema formation by inhibiting blood-brain barrier sodium transport. Dexamethasone was compared with progesterone since the latter is a more potent inhibitor of sodium transport in isolated capillaries. Sprague-Dawley rats were treated with vehicle (n=22) or 2 mg/kg of either dexamethasone (n=22) or progesterone (n = 17) 1 hour before occlusion of the middle cerebral artery. After 4 hours of ischemia, brain water content and blood-brain barrier permeability to [3H]α-aminoisobutyric acid and sodium-22 were determined. In controls, mean±SEM water content of tissue in the center of the ischemic zone was 82.4±0.2%. Brain edema was significantly reduced following pretreatment with either dexamethasone (80.6±0.1%, p<0.001) or progesterone (81.5±0.3%, p<0.05). There was also a significant reduction in blood—brain barrier permeability to α-aminoisobutyric acid in normal brain following either treatment (e.g., 2.21 ±0.19 and 1.37±0.10 µl/g/min, p< 0.001, for control and dexamethasone treatments, respectively), but no effect on the permeability to sodium (e.g., 1.19±0.05 and 1.12±0.11 µl/g/min for control and dexamethasone treatments, respectively). Furthermore, steroid treatment did not reduce blood-brain barrier permeability to sodium in ischemic brain (e.g., 2.53 ±0.39 and 2.40±0.33 µl/g/min for control and dexamethasone treatments, respectively). We conclude that pretreatment with dexamethasone and, to a lesser extent, progesterone reduces brain edema during the early stages of ischemia; however, this effect is not the result of reduced blood-to-brain sodium transport. © 1990 American Heart Association, Inc.