Objective To investigate the effects of recombinant tissue plasminogen activator (rt-PA)intravenous thrombolysis on blood-brain barrier (BBB) permeability,the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats.Methods A total of 40 adult male Sprague-Dawley rats were allocated into 3 groups:Sham operation group (n =10),middle cerebral artery occlusion (MCAO) group (n =18),and rt-PA thrombolysis group (n =18).A MCAO model was established by using autologous thromboembolism.The sham operation group did not inject any thromboembolus,the MCAO group only made MCAO,and the rt-PA thrombolysis group received intravenous thrombolysis with rt-PA at 3 hours after MCAO.Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride staining BBB permeability was measured by Evans blue dye leakage.The activities and the expressions of MMP-2 and MMP-9 in brain tissue were detected by Gelatin zymography and Western blot,respectively.Results Compared to the MCAO group,the neurological function was improved significantly in the rt-PA thrombolysis group,and the infarct volume was also reduced significantly (t =7.365,P =0.005).However,the hemorrhage score (t =-3.286,P =0.017) and BBB permeability (t =-3.947,P =0.029) were increased significantly.The activities and the expressions of MMP-2 and MMP-9 in the sham operation group were lower.The activities and the expressions of MMP-2 (t =-45.121,P =0.000; t =-11.624,P=0.000) and MMP-9 (t=-71.849,P=0.000; t=-8.992,P=0.000) in the MCAO group were increased and upregulated significantly.Compared to the MCAO group,the activities and the expressions of MMP-2 (t =-28.792,P =0.000; t =-3.809,P =0.013) and MMP-9 (t =-53.506,P =0.000; t =-2.640,P =0.046) in the rt-PA thrombolysis group were increased and upregulated significantly.Conclusions After rt-PA intravenous thrombolytic therapy,the BBB permeability was increased.The activities and the expressions of MMP-2 and MMP-9 were increased and upregulated.MMP-2 and MMP-9 might participate in the increased BBB permeability,and thus inducing hemorrhagic transformation after rt-PA intravenous thrombolytic therapy in rats with cerebral ischemia.

Objective To investigate the protective role of human serum albumin in treatment of monocyte-inducible C-type lectin (Mincle)-associated neuroinflammation in subarachnoid hemorrhage (SAH) rats and its underlying mechanisms.Methods Vascular perforation model was used to induce SAH.Ninety-two male SD rats were randomly assigned to sham (n =23),vehicle (n =23),low-dose albumin (0.63 g/kg,n =23) and high-dose albumin (1.25 g/kg,n =23) groups.Saline and albumin were intravenously injected into rats two hours after surgery.Modified Garcia scale was employed to assess neurological functions.Iba-1 and myeloperoxidase (MPO) staining was used to examine the activation of microglial cells and infiltration of neutrophils.Real-time PCR was applied to determine the changes of IL-1β,inducible nitric oxide synthase,CD11b,monocyte chemoattractant protein-1,cytokine-induced neutrophil chemoattractant-1 and CXC motif chemokine ligand-2 mRNA levels.Co-immunoprecipitation was conducted to assess the binding ability of albumin with Mincle.Immunoblotting was carried out to evaluate protein levels of Minlce,Syk and p-Syk.SAH severity measurement was performed before conductions of all the experiments.Results SAH severity scores were 11.4 ± 1.6,12.8 ±2.5 and 11.2 ±3.2 in the vehicle,low-dose albumin and high-dose albumin groups,respectively,without statistically significant difference among groups (F =0.694,P =0.516).Neurological score was 7.5 ± 2.9 in the vehicle group,while the low-dose albumin (14.6 ± 2.2) and high-dose albumin groups (13.6 ± 2.7) exhibited better neurological perfomance (P ＜ 0.01).Immunostaining showed that albumin significantly inhibited the activation of microglia,and reduced the percentage of MPO positive cells from 20.7％ ± 1.9％ in the vehicle group to 12.1％ ±2.1％ in the low-dose albumin group and 9.8％ ±0.9％ in the high-dose albunin group (F =32.216,P =0.001).mRNA levels of pro-inflammatory cytokines and chemotactic factors were also suppressed by albumin (P ＜ 0.05).The results of co-immunoprecipitation displayed that albumin could directly bind Mincle and disrupt the association between Mincle and SAP130.Immunoblotting demonstrated that albumin depressed the protein levels of Mincle,Syk and p-Syk.Conclusion Human serum albumin can inhibit Mincle/Syk-induced neuroinflammation via directly binding Mincle receptor in SAH rats.

Objective To investigate the relationship between osteoprotegerin ( OPG ) gene polymorphisms and susceptibility to large-artery atherosclerotic stroke ( LAA ). Methods A total of 1 010 patients with LAA registered in Nanjing Stroke Registry Program between August 2013 and May 2017 were retrieved, and 1 121 healthy residents were selected as controls. Two single nucleotide polymorphisms of rs2073617 and rs3134069 of OPG gene were genotyped by SNPscan technique. Multivariate logistic regression analysis was used to analyze the relationship between rs2073617/rs3134069 and susceptibility to LAA. Results Multivariate logistic regression analysis indicated that the rs3134069 C allele (odds ratio [OR] 1.39, 95%confidence interval [CI] 1.13-1.71; P=0.002) and its corresponding CC/CA genotype (OR 1.43, 95% CI 1.14-1.80; P=0.002) were the independent risk factors for LAA. Stratification analysis showed that this association was more pronounced in the subgroups of olderly (≥60 years), those with hypertension, smoking or without diabetes and hyperlipidemia. In addition, haplotype analysis showed that G-C haplotype of rs2073617/rs3134069 was also an independent risk factor for LAA onset (OR 1.36, 95% CI 1.10-1.68; P=0.005). Conclusion OPG gene polymorphisms are associated with the susceptibility to LAA.

The morbidity and mortality of stroke caused by large vessel occlusion are high,and its outcome is closely associated with emergency treatment.In order to receive treatment within the time window,the effective prehospital assessment is very important.The prehospital stroke scale simplifies emergency screening and assessment of such patients.Although the predictive value is good,its role remains controversial.This article reviews some of the prehospital stroke scales used to identify large vessel occlusions and analyzed the characteristics of different scales.

White matter lesion is a major subtype of cerebral small vessel disease. Its pathophysiology and mechanism remain unclear. Because the risk factors often coexist in clinical research, it is difficult to judge the relationship between certain risk factors and white matter injury. Moreover, due to the differences in animal and human brain tissue structure, there is currently a lack of reproducible animal models of white matter lesions. Therefore, establishing a practical animal model and further exploring the pathogenesis and risk factors of white matter lesions from the basic research level is crucial for the preclinical study of the treatment of white matter damage. This article reviews the characteristics, optimization measures, and application prospects of the white matter lesion models.

In early stage after liver transplantation(LT), coagulation function of recipients stays in a fragile balance. Affected by a variety of complex mechanisms, blood is usually hypercoagulable. An imbalance between coagulation factors and physiological anticoagulants, elevated level of vWF, an occurrence of fibrinolysis inhibition and dosing of immunosuppressive agents cause a hypercoagulable state in an early stage after LT. Blood hypercoagulability may lead to such thrombotic complications as hepatic artery, portal vein and deep vein thromboses. Some studies have demonstrated that postoperative prophylactic anticoagulation has some effect in reducing the risks of early postoperative thrombosis. However, there is still a great lack of high-quality evidence. This review summarized the latest researches on early coagulation dysfunction, thrombosis and preventive anticoagulation after LT.

Objective: To investigate the safety of argatroban in vertebral artery stenting and its effect on postoperative restenosis. Methods: From January 2013 to September 2017, patients undergoing vertebral artery stenting in the Department of Neurology, Jinling Hospital were enrolled prospectively. They were divided into agatraban group and heparin group by random number table method. The argatroban group received argatroban anticoagulation during the procedure, and was continuously used for 5 d after procedure; while the heparin group underwent heparin anticoagulation during the procedure, and used saline as placebo after procedure. Clinical follow-up was performed at 1, 3, and 6 months after procedure. Digital subtraction angiography, CT angiography, or magnetic resonance angiography were performed at 6 months to evaluate the restenosis of the treated blood vessels. The primary endpoints included intraoperative safety, in-stent restenosis after procedure, and any clinical events that occurred during the follow-up period, including stroke, cardiovascular events, and death. Major safety events included bleeding from various organs, allergic reactions, liver dysfunction, and embolism events. Kaplan-Meier survival curve was used to evaluate the incidence of vascular events during the follow-up period. Results: A total of 105 patients were enrolled in the analysis, including 53 in the argatroban group and 52 in the heparin group. During the periprocedural period, no hemorrhagic events, allergic reactions, liver dysfunction or embolism events occurred in both groups. There were no significant differences in preoperative vertebral artery stenosis degree, postoperative residual stenosis degree, and stenosis degree at 6 months after procedure between the two groups, but the increase of stent stenosis at 6 months after procedure in the agatroban group was significantly lower than that in the heparin group (13.56%±26.41% vs. 4.25%±15.76%; P=0.031). There was no significant difference in the incidence of stroke recurrence (P=1.000) and clinical events (P=0.739) between the two groups during the long-term follow-up period. Conclusions It is safe to use agatraban anticoagulant therapy in the vertebral artery stenting. Continuous use of agatraban anticoagulation after procedure may effectively reduce the increase of stent stenosis at 6 months after procedure.