Loss of AQP4 polarized localization with loss of β-dystroglycan immunoreactivity may induce brain edema following intracerebral hemorrhage

Abstract

The aquaporin-4 (AQP4) water channel contributes to brain water homeostasis in perivascular and subpial membrane domains of astrocytes where it is concentrated. These membranes form the interface between the neuropil and the extracellular liquid spaces. The brain-selective deletion of the dystroglycan (DG) gene causes a disorganization of AQP4 on the astroglial endfeet. First, we analyzed the expression of AQP4, β-DG in the brain following intracerebral hemorrhage (ICH) and correlated AQP4 expression with the expression pattern of the β-DG, which is a component of dystrophin-dystroglycan complex (DDC). Besides, the vessels ultrastructure and brain water content were investigated at different time points post-ICH (day 1, day 3, day 7). We found that AQP4 polarity was disturbed in parallel with the loss of β-DG in the perihematomal area post-ICH. At day 1 post-ICH, brain edema was obvious and the damage of vascular ultrastructure was the most severe. These results suggest a role for β-DG in targeting and stabilizing AQP4 channel in astrocytic cells, which may be critical for water homeostasis in brain.

Keywords: Aquaporin-4; Brain edema; Intracerebral hemorrhage; Polarity; β-Dystroglycan.