Journul 011 Neurochunislry zyxwvutsrqponml Raven Press, zyxwvutsrqponml Ltd., New York zyxwvutsrqponm 0 1989 International Society for Neurochemistry Acidosis, Acetazolamide, and Amiloride: Effects on 22Na Transfer Across the Blood-Brain and Blood-CSF Barriers Vincent A. Murphy and *Conrad E. Johanson Laboratory zyxwvutsrqpo of Neurosciences, National Institute on Aging, National Institutes zyxwv of Health, Bethesda, Maryland; and *Department of Ciinical Neurosciences, Program in Neurosrtrgery, Brown University and Rhode Island Hospital, Providence, Rhode Island, U.S.A. Abstract: Sprague-Dawley rats were given treatments, k ,nown to decrease 22Na movement into choroid plexus and CSF, to investigate their effect on "Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was in- jected intraperitoneally into bilaterally nephrectomize'd rats, and the rate of "Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe aci- dosis (arterial pH 7.2), produced by HCl injection, decireased the rate of 22Naentry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH&l injlection reduced brain entry by 1890, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of "Na into parietal cor- zyxwvut ~~ tex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of "Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is <30 min, the results indicate that both metabolic acidosis and amiloride decrease Na' per- meativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na' move- ment only across the choroidal epithelium. Key Words: Ce- rebral capillaries-Amiloride- Acetazolamide-Acidosis- ''Na uptake rate-Choroid plexus. Murphy V. A. and Jo- hanson zyxwv C. zyxwv E. Acidosis, acetazolamide, and amiloride: Effects on 22Na transfer across the blood-brain and blood-CSF bar- riers. J. Neurochem. 52, 1058-1063 (1989). The blood-brain barrier restricts the movement of polar solutes and ions into the CNS (Bradbury, 1979). The cerebral capillaries separate brain interstitial fluid from blood (Bradbury, 1985; Goldstein and Betz, 1986), whereas the choroid plexus and arachnoid membrane separate CSF from the systemic circul.ation (Johanson, 1989). The endothelial cells of the capil- laries, and the epithelial cells of the choroid plexus and arachnoid, are connected by tight junctions which re- strict paracellular movement of ions. In addition, transport systems that regulate the concentrations of ions and nutrients in brain interstitial fluid and CSF have been described for both the cerebral capill.aries and choroid plexus (Betz and Goldstein, 1986; Johan- son, 1989). Numerous studies on the entry of Na' into the CNS have been conducted, owing to the importance of this ion in osmotic regulation and fluid movement (Brad- bury, 1979). Na' enters the CNS across both the ce- rebral capillaries and the choroid plexus (Smith e:t al., 1982; Smith and Rapoport, 1986), but the majority enters across the choroidal epithelium due to active Na+ transport responsible for CSF formation (Davson and Segal, 1970; Wright, 1978) and more permeable tight junctions (Bouldin and Krigman, 1975). During initial entry of 22Na, a concentration gradient from ventricular CSF to brain interstitial fluid results, and so there is net diffusion of 22Nainto brain from CSF (Smith and Rapoport, 1986). Several studies of 22Na or 24Na uptake into brain assumed isotope transfer to be across the cerebral capillaries only, and ignored the contribution from CSF (Bradbury, 1979). Davson and Welch (1 97 1) used elaborate mathematic analysis to separate movement across the cerebral capillaries from other contributions, but this analysis required knowl- edge of parameters difficult to measure, such as brain interstitial fluid and CSF volumes. Recently, Smith and Rapoport ( 1986) have demonstrated for 36Cluptake that cortical regions distant from the choroid plexus are relatively free of isotope penetrating from CSF when Received April zyxwvutsrqp 12, 1988; revised manuscript received September 13, 1988; accepted September 15, 1988. Address correspondence and reprint requests to Dr. C. E. Johanson at Program in Neurosurgery, 593 Eddy Street, Rhode Island Hospital, Brown University, Providence, R1 02902, U.S.A. Abbrevialions used: CA, carbonic anhydrase; K,, , transfer rate; Vd, volume of distribution; VV, vascular volume. 1058