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 ischem ia is associated with an increase in both sodium content and blood-bra in barrier (BBB) sodium transport. The goals of this study were to det ermine whether chloride is the principal anion that accumulates in isc hemic brain, how the rate of BBB transport of chloride compares with i ts rate of accumulation, and whether the stimulation seen in BBB sodiu m transport is also seen with other cations. Focal ischemia was produc ed by occlusion of the middle cerebral artery (MCAO) in anesthetized r ats. Over the first 6 h after MCAO, the amount of brain water in the c enter 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 (3 4 +/- 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 cati ons. 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-a minoisobutyric acid (H-3]AIB) and [C-14]urea} was determined. Permeabi lity to either passive tracer was not increased, indicating that the B BB was intact. The rate of Cl-36 influx was 3 times greater and the ra te of Na-22 influx 1.8 times greater than their respective net rates o f accumulation in ischemic brain. The BBB permeability to Na-22 relati ve to that of [H-3]AIB was significantly increased in the ischemic cor tex, the relative permeability to Rb-86 was significantly decreased, a nd the relative permeability to Cl-36 was unchanged. These results ind icate that the stimulation in BBB sodium transport is specific for sod ium. Further, chloride accumulates with sodium in brain during the ear ly stages of ischemia; however, its rate of accumulation is low compar ed with its rate of transport from blood to brain. Therefore, inhibiti on of BBB sodium transport is more likely to reduce edema formation th an is inhibition of BBB chloride transport.