AIM:To investigate the effects of propofol on ammonia-induced neocortical astrocyte aquaporin-4 expression in rats and its mechanism. METHODS:Astrocytes were separated from newborn Sprague Dawley rats. Glial fibrillary acidic protein,the specific protein of astrocyte,was labeled by cell immunofluorescence method. The purity of astrocyte achieved to 95% was considered to be used in the study. Grouping:cultured astrocytes were randomly divided into 5 groups (n=3):normal control group (N); ammonia-incubated for 24 h group (NH_4Cl-24 h); p38 antagonist SB203580 (10 μmol/L) pretreated group (SB); propofol (10 μmol/L) pretreated group (P); solvent (DMSO) control group (C). SB203580,propofol and DMSO were pretreated for 30 min before astrocytes were exposed to NH_4Cl. Cell morphology was assessed by light microscopy. The expression of aquaporin-4; p38 and p-p38 were detected by Western blotting. RESULTS:Astrocytes were found significant swelling when exposed to 5 mmol/L NH_4Cl in NH_4Cl-24 h group compared to control group. Pretreatment with propofol and SB203580 decreased astrocyte swelling. No significant change in total p38 in all groups was observed (P>0.05) by Western blotting analysis,while the levels of p-p38 and AQP4 in group SB and group P were significantly decreased compared to group C and group NH_4Cl-24 h (P<0.05).CONCLUSION:The expression of AQP4 is regulated by p38 pathway. Propofol pretreatment down-regulates aquaporin-4 expression through preventing the ammonia-induced p38 phosphorylation.