Effect Of Gap Junction Blocker Carbenoxolone On Blood Brain Barrier Of Rat Brain During Cerebral Ischemia Reperfusion

Objective: To study the effect of carbenoxolone, the specific inhibitor of gap junction, onthe permeability of blood brain barrier, cerebral edema and expression of blood brainbarrier junctional complex related protein during cerebral ischema reperfusion.Methods: SD rats were subjected to middle cerebral artery occlusion (MCAO) to inducefocal ischemia. After MCAO, the rats in experimental group were injected with gapjunction blocker CBX; Those in ischemic control group were injected with normal salineand blank control group did not receive treatment. Then respectively, for the followingresearch:(1) Evans Blue assay was used to determinate the change of permeability of bloodbrain barrier.(2) MRI was applied to evaluate the degree of brain edema.(3)Immunofluorescence staining was performed to analyze the effect of CBX on protein(VE-cadherin, ZO-1, Claudin5) expression.Results: The content of EB of the brain tissue was（317.60±1.31）ng/g in the CBXintervention group and(975.29±1.23）ng/g in the control group respectively. The EBcontent in CBX treament group was lower than that of the control group(P <0.05). TheADC value was（6.14±0.39）×10-4mm2/s in the infarction district of the CBXgroup and(6.93±0.29)×10-4mm2/s in the contralateral corresponding area.In the control group,theADC value was（5.91±0.86）×10-4mm2/s in the infarction district and（7.79±0.37）×10-4mm2/s in the contralateral corresponding area. The rADC value is in the range of70.6%to96.3%in the CBX intervention group, while it was62.6%-87.0%in the control group.Both the ADC values and the rADC value of the infarction distict in the CBX group werehigher than those in control group (P <0.05). After CBX treatment, protein expression of Claudin-5, ZO-1and VE-cadherin were increased compared with thhose in control group (P<0.05).Conclusion: The gap junction blocker CBX has protective effect on the blood brain barrierduring cerebral ischemia reperfusion injury. CBX could reduce the damage of blood brainbarrier permeability, as well as brain edema.Meanwhile the expression of the BBB’sjunctional complex related proteins were also up-regulated after CBX intervention.