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This study examined whether levetiracetam inhibits Ncbe\/NBCn2\u2010mediated transport and alters cerebrospinal fluid acid\u2013base balance, transporter abundance, and cerebrospinal fluid secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Ncbe and NBCn1 activity was assessed in heterologous expression systems as Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent pH recovery after intracellular acidification. Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent pH recovery was also measured in isolated mouse choroid plexus epithelial cells. Cerebrospinal fluid pH and apparent secretion rate were assessed in\u00a0vivo after levetiracetam treatment. Acetazolamide was included as a pharmacological control for inhibition of HCO\n                      <jats:sub>3<\/jats:sub>\n                      <jats:sup>\u2212<\/jats:sup>\n                      \u2010dependent secretion. Transporter abundance was assessed by immunoblotting, and molecular docking was used to explore interactions between levetiracetam, Ncbe and related\n                      <jats:italic>SLC4A<\/jats:italic>\n                      transporters.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Levetiracetam inhibited Ncbe\u2010mediated transport, whereas no levetiracetam\u2010sensitive NBCn1\u2010mediated component was detected under the same experimental conditions. In choroid plexus epithelial cells, levetiracetam reduced Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent pH recovery to a similar extent as pharmacological inhibition of stilbene\u2010sensitive transport. After 5\u2009days of treatment, levetiracetam was associated with lower cerebrospinal fluid pH and a higher apparent cerebrospinal fluid secretion rate compared with control mice. Levetiracetam reduced Ncbe and NBCe2 abundance, while aquaporin\u20101 abundance increased. Molecular docking predicted levetiracetam interactions with residues involved in Na\n                      <jats:sup>+<\/jats:sup>\n                      and HCO\n                      <jats:sub>3<\/jats:sub>\n                      <jats:sup>\u2212<\/jats:sup>\n                      coordination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings identify Ncbe as a levetiracetam\u2010sensitive HCO\n                      <jats:sub>3<\/jats:sub>\n                      <jats:sup>\u2212<\/jats:sup>\n                      transporter in the choroid plexus and support effects on cerebrospinal fluid acid\u2013base balance and secretion.\n                    <\/jats:p>\n                  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