Figure 2

Schematic summary of a beneficial role AQP4 upregulation plays during the edema resolution phase. The upregulation of AQP4 causes increased water clearance from the tissue, which in turn causes decreased BBB disruption because of decreased pressure, and there is less neutrophil infiltration and decreased pro-inflammatory cytokines. This cause decreased MMP production [62], which possibly results in less destruction of the basal lamina and tight junctions, causes an even greater decrease of the BBB. In another pathway (dotted lines), the increased water clearance from the tissue and extracellular space causes changes in the osmotic pressure, changing the activation state of the stretch activated ion channels expressed in microglia [86–88], causing less microglial activation, thus causing decreased pro-inflammatory cytokine. The resulting decrease in BBB disruption/permeability leads to decreased vasogenic edema or better edema resolution. Finally, this scheme outlines the potential link between AQP4, edema and neuroinflammation.