We further confirmed that in addition to its osmotic force, 3% NaCl could inhibit expression www.selleckchem.com/products/Calcitriol-(Rocaltrol).html of IL 1b and TNFa, alleviate disruption of the BBB and reduce cerebral edema induced by LPS. AQP4 is a water channel protein predominantly expressed in astrocyte foot processes at the borders Inhibitors,Modulators,Libraries between the brain parenchyma and major fluid compart ments, and in Inhibitors,Modulators,Libraries ependymal cells lining the ventricles in contact with cerebrospinal fluid in the brain. This distribution suggests that AQP4 probably participates in water fluxes into and out of the brain parenchyma. AQP4 is up regulated in the brain in ischemic brain edema. AQP4 probably plays a critical role in reabsorp tion of cerebrospinal fluid and regulation of brain edema.

AQP4 null mice have lower mortality and are less prone to cytotoxic brain edema, including water intoxica tion cerebral edema, early Inhibitors,Modulators,Libraries focal cerebral ischemia and bacterial meningitis. Accordingly, overex pression of AQP4 in transgenic mice accelerates progres sion of cytotoxic brain swelling. Down regulation of AQP4 could be a way in which HS ameliorates cerebral edema. AQP4 down regulation slows the rate of water entry into the brain in cytotoxic edema. Our results show that injection of LPS could up regulate expression of AQP4 mRNA and protein, which is consis tent with previous reports. Our results also showed for the first time that 3% NaCl could down investigated the effect of HS on AQP4 expression induced by IL 1b in astrocytes in vitro to explore the mechanism of HS down regulation of brain AQP4.

The results show that IL 1b significantly increased the AQP4 mRNA and membrane protein level in the astrocytes in vitro and that 3% NaCl attenuated the increase of AQP4 mRNA and protein induced by IL 1b. These results indicate that 3% NaCl also directly Inhibitors,Modulators,Libraries antagonizes the IL 1b action of inhibiting up regulated expression of AQP4 in the astrocytes. This may be another mechanism by which 3% NaCl inhibits the up regulation of AQP4 expression induced by LPS. PKC serves as a second messenger for G protein recep tors that are coupled to the phosphoinositide pathway, causing Inhibitors,Modulators,Libraries either a transient rise in intracellular Ca2. through inositol triphosphate or activating PKC through diacylglycerol. Previous studies have shown that activa tion of PKC decreases the expression of AQP4 in rat astrocytes and attenuates AQP4 up regulation and brain edema formation.

Pretreatment of the cultured rat astrocytes inhibitor Gefitinib with cyclo heximide or actinomy cin D does not change the decrease in AQP4 mRNA induced by the phorbol ester 12 O tetradecanoylphorbol 13 acetate. It is sug gested that PKC may be involved in AQP4 regulation on the transcriptional level, rather than affecting de novo protein synthesis or the stability of AQP4 mRNA. Tang et al. reported that thrombin inhibits AQP4 expression through a PKC dependent pathway in cultured astrocytes.