Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats.

Abstract

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 [ 3 H]«-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 a-aminoisobutyric acid in normal brain following either treatment (e.g., 2.21 ±0.19 and 1.37±0.10 /il/g/min,/><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 /il/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 /il/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. (Stroke 1990;21:1199-1204)

Blood—Brain Barrier Permeability and Brain Concentration of Sodium, Potassium, and Chloride during Focal Ischemia

“…Surprisingly, the rate of sodium flux from blood to brain is accelerated in ischemia relative to pas sive perm e ability tracers as shown in the present study (Fig. 4) and previously (Betz and Coester, 1990;Ennis et aI., 1990;Schielke et aI., 1991;Dick inson and Betz, 1992). Since brain capillary Na,K ATPase is likely to provide the driving force for blood-to-brain sodium transport (Betz, 1986;Schielke and Betz, 1992) and since the activity of this transporter can be increased by a rise in the extracellular potassium concentration , we have speculated that the elevated po tassium concentration in the interstitial fluid of brain during ischemia stimulates blood-to-brain so dium transport by enhancing brain capillary Na,K ATPase activity (Schielke et aI., 1991).…”

“…However, we have recently shown that there is spread of edema fluid in this model from the center of the ischemic zone to surround ing, less ischemic tissue. Based upon previous stud ies (Betz and Coester, 1990;Martz et aI., 1990;Menzies et aI., 1993), we estimate that 50% of the total edema that forms in the ischemic cortex is located outside of the center of the ischemic zone. Thus, some of the sodium that enters the brain in the ischemic core may not accumulate there, but rather in the adjacent tissue, which was not sampled The specific permeability of sodium, rubidium, and chloride relative to u-aminoisobutyric acid (AlB).…”

“…Previous studies have shown that the integrity of the BBB is normal 3-4 h after MCAO (Betz and Coester, 1990;Martz et aI., 1990;Schielke et aI., 1991) but increases progres sively following 6 h of ischemia (Menzies et aI., 1993). For the present study, we used two different tracers that cross the BBB by simple diffusion, AIB and urea, to assess BBB integrity.…”

“…dium accumulates in brain is similar in magnitUde to the rate of transport of sodium from blood to brain across the blood-brain barrier (BBB) (Betz et aI., 1989). Furthermore, the permeability of the BBB to sodium increases well before the passive permeabil ity of the BBB increases during ischemia (Betz and Coester, 1990;Ennis et aI., 1990;Schielke et aI., 1991;Dickinson and Betz, 1992). It has been hy pothesized that this increase may result from a stim ulation of Na,K-ATPase in the brain capillary either through free radical-mediated capillary injury (Go toh et aI., 1985) or through the elevated extracellu lar potassium concentration in brain (Schielke et aI., 1991).…”

Mechanisms of Brain Ion Homeostasis during Acute and Chronic Variations of Plasma Potassium

“…The permeability of the BBB to 22 Na + was as sessed by a modification of the method proposed by Ohno et al (1978) for a single time point analysis as previously described (Betz and Coester, 1990). A bolus of 0.2 ml saline containing 15 fLCi 22 Na + was injected intravenously 10 min before decapitation of rats rendered acutely or chronically hypo-or hyper kalemic (n = 5-7 in each group).…”