MECHANISMS OF SODIUM-TRANSPORT AT THE BLOOD-BRAIN-BARRIER STUDIED WITH IN-SITU PERFUSION OF RAT-BRAIN

The mechanism of unidirectional transport of sodium from blood to brai n in pentobarbital-anesthetized rats was examined using in situ perfus ion. Sodium transport followed Michaelis-Menten saturation kinetics wi th a V-max of 50.1 nmol/g/min and a K-m of 17.7 mM in the left frontal cortex. The kinetic analysis indicated that, at a physiologic sodium concentration, similar to 26% of sodium transport at the blood-brain b arrier (BBB) was carrier mediated. Dimethylamiloride (25 mu M), an inh ibitor of Na+/H+ exchange, reduced sodium transport by 28%, whereas ph enamil (25 mu M), a sodium channel inhibitor, reduced the transfer con stant for sodium by 22%. Bumetanide (250 mu M) and hydrochlorothiazide (1.5 mM), inhibitors of Na+-K+-2Cl(-)/NaCl symport, were ineffective in reducing blood to brain sodium transport. Acetazolamide (0.25 mM), an inhibitor of carbonic anhydrase, did not change sodium transport at the BBB. Finally, a perfusate pH of 7.0 or 7.8 or a perfusate PCO2 of 86 mm Hg failed to change sodium transport. These results indicate th at 50% of transcellular transport of sodium from blood to brain occurs through Na+/H+ exchange and a sodium channel in the luminal membrane of the BBB. We propose that the sodium transport systems at the lumina l membrane of the BBB, in conjunction with CL(-)/HCO3- exchange, lead to net NaCl secretion and obligate water transport into the brain.