Downregulation of NF-κB by Shp-1 alleviates cerebral venous sinus thrombosis-induced brain edema via suppression of AQP4

Aquaporin 4 (AQP4), a water channel protein, has been well studied in arterial stroke-induced brain edema. However, the role of AQP4 in cerebral venous sinus thrombosis (CVST) has not been reported. Here, we showed that AQP4 expression was increased in the brain of a rat CVST model, whereas inhibition of AQP4 decreased cerebral edema. Subsequent experiments showed that Shp-1 (Src homology 2-containing phosphatase-1) expression and NF-kappa B phosphorylation were upregulated after CVST. We found that Shp-1 inhibition resulted in enhancement of NF-kappa B activation and increased AQP4 expression accompanied by aggravated brain edema. We further showed that NF-kappa B inhibition led to decreased AQP4 expression and subsequent attenuation of brain edema but had no significant effect on Shp-1 expression. These results provide the first evidence suggesting that downregulation of NF-kappa B by Shp-1 alleviates CVST-induced brain edema through suppression of AQP4.