Effect of mast cell activation on the blood-brain barrier injury after subarachnoid hemorrhage in rats
Objective To investigate the effect and mechanism of mast cells(MCs)activation on blood-brain barrier(BBB)injury after subarachnoid hemorrhage(SAH)in rats.Methods The SAH mod-el was prepared by intravascular perforation.A total of 80 adult male Sprague-Dawley rats were divided into 8 groups of 10 rats in each group according to the random number table method.The other 66 rats were ran-domly divided into sham group,SAH group and cromolyn sodium(CRO)group according to the numerical table method,with 22 rats in each group.The CRO group was injected with 25 mg/kg CRO intraperitoneal-ly immediately after surgery,and the SAH group was injected with the same volume of normal saline.SAH score,neurological function score,brain water content measurement,Evans blue staining and open field test were performed 8 h after surgery.Toluidine blue staining and immunohistochemical staining were used to detect MCs activation.Western blotting was used to detect the expression of claudin-5,ZO-1,Occludin,and tryptase.The t-test was used for comparison between groups.The Paired t-tests were used for compari-sons between groups.Results The expression of tryptase and the activation of MCs peaked 8 h after sub-arachnoid hemorrhage in rats.Evans blue staining in the SAH group was darker than that in the sham group and the Cro group.The neurological function score of the SAH group was lower than that of the sham group and the CRO group(12.90±0.89 vs.18.00±0,15.80±1.26,t=9.75,2.47,P<0.05).The cere-bral water content of the SAH group was higher than that of the sham group and the CRO group(79.69±0.13 vs.78.47±0.17,79.22±0.12,t=11.16,5.38,P<0.05).The number of entries and exits in the SAH group and the distance of movement in the center were lower than those in the sham group and the CR0 group(6.80±3.11 vs.19.00±6.04,14.40±5.94,t=4.04,2.53,P<0.05),(0.44±0.09 vs.0.96±0.20,0.86±0.20,t=4.33,4.12,P<0.05).The central time in the SAH group was longer than that in the sham group and the CRO group(153.40±44.42 vs.93.60±15.11,52.20±20.63,t=2.85,4.62,P<0.05).The expression of ZO-1 in the SAH group was lower than that in the sham group and the CRO group(0.25±0.10 vs.0.63±0.05,0.51±0.08,t=5.91,3.45,P<0.05).The ex-pression of Occludin was lower in the SAH group than that in the sham group and the CRO group(0.18±0.01 vs.0.67±0.07,0.46±0.07,t=12.40,7.21,P<0.05),and that of Claudin-5 was lower than that in the sham group and the CR0 group(0.45±0.03 vs.1.25±0.04,0.67±0.07,t=27.52,4.85,P<0.05).The Tryptase in the SAH group was higher than that in the sham group and the CRO group(0.60±0.01 vs.0.33±0.01,0.42±0.01,t=28.13,20.31,P<0.05).Conclusion The activation of MCs peaked at 8 h after SAH in rats.The activation of MCs promoted the disruption of the BBB and me-diated early brain injury,and the mast cell stabilizer CRO inhibited the activation of MCs to alleviate the disruption of the BBB and improve neurological function in rats.