Objective To investigate the effect of hypertonic saline on the expressions of aquaporin 4 (AQP4) and caspase-3 in the brain edema area after traumatic brain injury (TBI) in rats Methods Seventy-two male SD rats weighing 220-250 g were selected and randomly divided into three groups (24 rats per group):sham operation group (Group A),traumatic brain injury + normal saline group (Group B) and traumatic brain injury + hypertonic saline group (Group C).Moderate TBI model was induced by Feeney's free falling method.Normal saline and hypertonic saline were delivered respectively.The neurological score was measured at 6,24,and 48 hours after operation.The brain water content was measured,and the blood brain barrier stability was detected by Evans blue staining.AQP4 positive cells was detected by immunohistochemistry.The expressions of AQP4 and caspase-3 protein in brain tissue were detected by Western blot,and the apoptosis of neurons in brain tissue by TUNEL method.Results Compared with Group A,the neurological score of Group B were obviously decreased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.73 ±0.31 vs.0.33 ±0.13;24 hours:2.47 ±0.27 vs.0.33 ±0.14;48 hours:2.18 ± 0.19 vs.0.33 ±0.12),caspase-3 protein expression(6 hours:0.53 ±0.18 vs.0.34 ±0.07;24 hours:0.58 ±0.16 vs.0.33 ± 0.08;48 hours:0.59 ± 0.11 vs.0.33 ± 0.07) and apoptosis index in brain tissue in Group B were significantly increased (all P ＜ 0.05).Compared with Group B,the neurological score of Group C were obviously increased,while the water content in the brain tissue,Evans blue staining,AQP4 positive cells,AQP4 (6 hours:1.51 ±0.27 vs.1.73 ±0.31;24 hours:2.13 ±0.13 vs.2.47±0.27;48 hours:1.84 ±0.22 vs.2.18 ±0.19) and Caspase-3 protein expression (6 hours:0.44±0.09vs.0.53±0.18;24 hours:0.46±0.10vs.0.58±0.16;48 hours:0.48±0.12 vs.0.59 ± 0.11) and apoptosis index in brain tissue of Group C were significantly decreased (all P ＜ 0.05).Conclusion Hypertonic saline can attenuate TBI-induced brain edema and have a significant neuroprotective effect,possibly by down-regulating the expressions of AQP4 and caspase-3.