Background:Disruption of the blood brain barrier(BBB)integrity at the early stage of ischemia is becoming a critical target to reduce hemorrhage transformation(HT)because of the potential to predict HT.However,the mec...Background:Disruption of the blood brain barrier(BBB)integrity at the early stage of ischemia is becoming a critical target to reduce hemorrhage transformation(HT)because of the potential to predict HT.However,the mechanism underlying early BBB damage is not very clear.It was reported that after acute ischemia,there was a significant increase of dopamine release in striatum where we have reported BBB damage as well as upregulation of HIF-1αafter 2 h ischemia.Objective:In current study,we aimed to investigate the role of dopamine signal pathway in BBB damage after acute ischemia using in vivo rat middle cerebral artery occlusion(MCAO)model.Results:Our data showed that there was an increase of endogenous tissue plasminogen activator(tPA)in BBB damage area and intra-striatum infusion of tPA inhibitor neuroserpin,significantly alleviated ischemia-induced BBB damage.In addition,intra-striatum infusion of D1 antagonist SCH23390 significantly decreased ischemia-induced upregulation of endogenous tPA,accompanied by decrease of BBB damage and occludin degradation.More important,inhibition of HIF-1 with inhibitor YC-1 significantly decreased acute ischemia-induced endogenous tPA upregulation and BBB damage.Conclusion:Taken together,our data demonstrate that acute ischemia disrupted BBB through activation of endogenous tPA via HIF-1 upreguationinduced dopamine increase,thus representing a new therapeutic target for protecting BBB,and may help alleviate HT following thrombolysis after ischemia stroke.展开更多
Objective To measure the concentration of D-dimer (DD), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen (PLG) activity in plasma and cerebrospinal fluid in patients with ...Objective To measure the concentration of D-dimer (DD), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen (PLG) activity in plasma and cerebrospinal fluid in patients with acute cerebral infarction and to investigate their clinical significance.Methods The concentrations of D-dimer, t-PA, and PAI-1 in plasma and cerebrospinal fluid in patients were measured by enzyme-linked immunosorbent assay (ELISA). The PLG biological activity was detected using the chromophore method. The results were compared with those of the controls.Results The concentrations of D-dimer, t-PA and PAI-1 in cerebrospinal fluid and plasma in patients with acute cerebral infarction were much higher than those of normal subjects (P<0.01). Conversely, the level of PLG activity was significantly lower in the patients than in the controls (P<0.01).Conclusion Hypercoagulability and secondary hyperfibrinolysis exist in patients with acute cerebral infarction.展开更多
文摘Background:Disruption of the blood brain barrier(BBB)integrity at the early stage of ischemia is becoming a critical target to reduce hemorrhage transformation(HT)because of the potential to predict HT.However,the mechanism underlying early BBB damage is not very clear.It was reported that after acute ischemia,there was a significant increase of dopamine release in striatum where we have reported BBB damage as well as upregulation of HIF-1αafter 2 h ischemia.Objective:In current study,we aimed to investigate the role of dopamine signal pathway in BBB damage after acute ischemia using in vivo rat middle cerebral artery occlusion(MCAO)model.Results:Our data showed that there was an increase of endogenous tissue plasminogen activator(tPA)in BBB damage area and intra-striatum infusion of tPA inhibitor neuroserpin,significantly alleviated ischemia-induced BBB damage.In addition,intra-striatum infusion of D1 antagonist SCH23390 significantly decreased ischemia-induced upregulation of endogenous tPA,accompanied by decrease of BBB damage and occludin degradation.More important,inhibition of HIF-1 with inhibitor YC-1 significantly decreased acute ischemia-induced endogenous tPA upregulation and BBB damage.Conclusion:Taken together,our data demonstrate that acute ischemia disrupted BBB through activation of endogenous tPA via HIF-1 upreguationinduced dopamine increase,thus representing a new therapeutic target for protecting BBB,and may help alleviate HT following thrombolysis after ischemia stroke.
文摘Objective To measure the concentration of D-dimer (DD), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen (PLG) activity in plasma and cerebrospinal fluid in patients with acute cerebral infarction and to investigate their clinical significance.Methods The concentrations of D-dimer, t-PA, and PAI-1 in plasma and cerebrospinal fluid in patients were measured by enzyme-linked immunosorbent assay (ELISA). The PLG biological activity was detected using the chromophore method. The results were compared with those of the controls.Results The concentrations of D-dimer, t-PA and PAI-1 in cerebrospinal fluid and plasma in patients with acute cerebral infarction were much higher than those of normal subjects (P<0.01). Conversely, the level of PLG activity was significantly lower in the patients than in the controls (P<0.01).Conclusion Hypercoagulability and secondary hyperfibrinolysis exist in patients with acute cerebral infarction.
