Aqp4 Expression And The Relationship Of The Blood-brain Barrier Permeability After Cerebral Ischemia And Reperfusion

Object:This work was to investigate the changes of AQP4 expression after cerebral ischemic reperfusion (CIR), and to study the relationship between the formation of the ischemic edema and the changes of AQP4 expression.Methods:A totle of 105 healthy Wistar rats were divided into 2 groups randomly, the CIR group and the sham operation control group. CIR models were established by occluding unilateral middle cerebral artery (MCA) of the rats with the suture method. The sutures were removed after 2 hours to allow reperfusion. The operation of the control group was as same as the CIR group except for occluding unilateral MCA. The brains of the animals were taken out at 6h,12h,24h,48h and 72h after reperfusion. Subsequently, the marphological changes were observed with HE staining. The expression of AQP4 and its mRNA was detected with IHC and ISH. The wet-dry weighing method was used to detect the brain water content.Results:There were no significant changes of the brain water content, the marphological changes and AQP4 expression in the control group. HE staining showed that the brain tissue had ischemic changes after reperfusion. The space around neurons and the capillaries became larger, some of the neurons were necrosis, the nuclei were deeply stained or disappeared and the number of the neurogliocyte increased. The expression of AQP4 was positive in the hippocampus,supraoptic nuclei,subfornical organ,area postrema,choroid plexes and other regions in IHC and ISH. The cytomembrane of the positive cells was stained, the cytoplasm and nuclei kept unstained in IHC. However, the cytoplasm was also stained but lighter than that of the cytomembrane in ISH. After reperfusion, the expression of AQP4 up-regulated, and finally reached a peak at CIR48~72h. The brain water content of ischemic brain tissue increased from CIR6h, and reached its peak also at CIR48~72h. The brain water content and AQP4 expression all reached its peak at CIR48~72h.Conclusions:Both the expression of AQP4 and the brain water content of the ischemic tissue increased after reperfusion. The results imply that AQP4 would have a close relationship with the formation of brain edema after CIR. AQP4 may play an important role in the formation and development of brain edema.