BLOOD-BRAIN-BARRIER PERMEABILITY AND BRAIN CONCENTRATION OF SODIUM, POTASSIUM, AND CHLORIDE DURING FOCAL ISCHEMIA

Brain edema formation during the early stages of focal cerebral ischemia is associated with an increase in both sodium content and blood-brain barrier (BBB) sodium transport. The goals of this study were to determine whether chloride is the principal anion that accumulates in ischemic brain, how the rate of BBB transport of chloride compares with its rate of accumulation, and whether the stimulation seen in BBB sodium transport is also seen with other cations. Focal ischemia was produced by occlusion of the middle cerebral artery (MCAO) in anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in the center of the ischemic cortex increased progressively at a rate of 0.15 +/- 0.02 (SE) g/g dry wt/h. This was accompanied by a net increase in brain sodium (48 +/- 12 mu mol/g dry wt/h) and a loss of potassium (34 +/- 7 mu mol/g dry wt/h). The net rate of chloride accumulation (16 +/- 1 mu mol/g dry wt/h) approximated the net rate of increase of cations. Three hours after MCAO, the BBB permeability to three ions (Na-22, Cl-36, and Rb-86) and two passive permeability tracers {[H-3]alpha-aminoisobutyric acid (H-3]AIB) and [C-14]urea} was determined. Permeability to either passive tracer was not increased, indicating that the BBB was intact. The rate of Cl-36 influx was 3 times greater and the rate of Na-22 influx 1.8 times greater than their respective net rates of accumulation in ischemic brain. The BBB permeability to Na-22 relative to that of [H-3]AIB was significantly increased in the ischemic cortex, the relative permeability to Rb-86 was significantly decreased, and the relative permeability to Cl-36 was unchanged. These results indicate that the stimulation in BBB sodium transport is specific for sodium. Further, chloride accumulates with sodium in brain during the early stages of ischemia; however, its rate of accumulation is low compared with its rate of transport from blood to brain. Therefore, inhibition of BBB sodium transport is more likely to reduce edema formation than is inhibition of BBB chloride transport.