Removal of aquaporin-4 from glial and ependymal membranes causes brain water accumulation

- Aquaporin-4 (AQP4) water channels in astrocytes regulate basal brain water content.
- AQP4 is not involved in draining CSF through arachnoid villi or lymphatic vessels.
- Ependymal AQP4 does not have any major effect on basal brain water content.

There is a constitutive production of water in brain. The efflux routes of this excess water remain to be identified. We used basal brain water content as a proxy for the capacity of water exit routes. Basal brain water content was increased in mice with a complete loss of aquaporin-4 (AQP4) water channels (global Aqp4−/− mice), but not in mice with a selective removal of perivascular AQP4 or in a novel mouse line with a selective deletion of ependymal AQP4 (Foxj1-Cre:Aqp4flox/flox mice). Unique for the global Aqp4−/− mice is the loss of the AQP4 pool subjacent to the pial membrane. Our data suggest that water accumulates in brain when subpial AQP4 is missing, pointing to a critical role of this pool of water channels in brain water exit.