The Role Of Aqp4 In Astrocyte Water Transport

Objective: This study was to investigate the expression of AQP4 during the pathological course of hemorrhagic cerebral edema in rats, and to study the relationship between AQP4 expression and brain edema formation following intracerebral hemorrhage (ICH). Methods: The Wistar rats were divided into two groups randomly, the control group and the ICH group. The experimental ICH model was established by infusing collagenase into the rat left caudate nucleus, the operation process of the control group was the same as the ICH group except for infusing collagenase. Each group was examined at interval times of 6h, 1d, 3d, 5d and 7d, respectively. AQP4 protein expression was measured by immunohistochemistry (IHC). AQP4mRNA expression was examined by in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR). Brain water content (BWC) was measured by wet-dry weighing method. The pathological changes in the edematous tissues were observed by light microscope, transmission electron microscope (TEM) and angiography.Results: There was no significant increase of BWC in the control group. The marked increase of BWC was at 6h after ICH, the peak at 3d, and the brain edema did not disappear at 7d after ICH (p<0.05). There was no significant change of AQP4 expression in the control group. Compared with control group, the expression of AQP4 mRNA and protein increased significantly in the edematous tissues at 6h after ICH, then reached a peak at 3d. In one week following ICH, it was still higher than the control level(p<0.01). The expression of AQP4 protein was positively correlated with AQP4mRNA during the brain edema formation (r >0.8281, p <0.01). The expression of AQP4 was positively correlated with BWC after ICH(r >0.9157, p<0.01). The corresponding sequential pathological changes were a gradual increase of intracellular edema(with 1-2d), then the brain edema became remarkable at 3d, an emergence of vasogenic edema, local edema tissue degeneration and necrosis. At 7days, the number of newborn capillaries in perihematomal tissues was increasing, and the brain edema became unremarkable.Conclusions: The increased expression of AQP4 after intracerebral hemorrhage may participate in the course of ICH, suggesting that AQP4 play an important role in the pathological course of the hemorrhagic brain edema, and inhibitor of AQP4 may be useful target for therapeutic intervention.