Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin‐1

Aquaporin‐1 (AQP1) is a water channel expressed strongly at the ventricular‐facing surface of choroid plexus epithelium. We developed novel methods to compare water permeability in isolated choroid plexus of wild‐type vs. AQP1 null mice, as well as intracranial pressure (ICP) and cerebrospinal fluid (CSF) production and absorption. Osmotically induced water transport was rapid in choroid plexus from wild‐type mice and reduced by fivefold by AQP1 deletion. AQP1 deletion did not affect choroid plexus size or structure. By stereotaxic puncture of the lateral ventricle with a microneedle, ICP was 9.5 ± 1.4 cm H2O in wild‐type mice and 4.2 ± 0.4 cm H2O in AQP1 null mice. CSF production, an isosmolar fluid secretion process, was measured by a dye dilution method involving fluid collections using a second microneedle introduced into the cisterna magna. CSF production in wild‐type mice was (in µl min–1) 0.37 ± 0.04 (control), 0.16 ± 0.03 (acetazolamide‐treated), and 1.14 ± 0.15 (forskolin‐treated), and reduced by ~25% in AQP1 null mice. Pressure‐dependent CSF outflow, measured from steady‐state ICP at different ventricular infusion rates, was not affected by AQP1 deletion. In a model of focal brain injury, AQP1 null mice had remarkably reduced ICP and improved survival compared with wild‐type mice. The reduced ICP and CSF production in AQP1 null mice provides direct functional evidence for the involvement of AQP1 in CSF dynamics, suggesting AQP1 inhibition as a novel option for therapy of elevated ICP.