| Purpose:The red cells composition of thrombi was detectable with MRI-GRE imaging in patients with isolated brainstem infraction caused by different mechanisms,showing a hypo intense signal whose diameter should exceed the diameter of occlusive parent vessel on GRE,called the MR susceptibility sign(SVS).SVS is quite useful to identify the intra-arterial clot,especially red erythrocyte-fibrin clots composed of deoxyhemoglobin that are more prevalent in cardiac emboli and dissection.As the mechanism of isolated brainstem infraction is still unclear,it is crucial to detect the composition of the thrombus in isolated brainstem infraction with large artery occlusion disease(LAOD).The aim of this study was to explore the SVS in patients with isolated brainstem infraction and posterior circulation large artery occlusion.Content:This was a single-center retrospective study.We have developed a strict set of criteria to evaluate whether the patient could match the requirement,including all of the patient’s imaging(CT,MRI,CTA,MRA or DSA).A neurologist and another neuroimaging expert would review all the cases of imaging to determine the existence of SVS(pontine infraction and medullary infraction)and stroke subtypes(atrial fibrillation,dissection,large artery atherosclerotic disease(LAAD)and undetermined).Methods:Comparisons of baseline characteristics(age,gender,hypertension,dyslipidemia,smoking history and diabetes)involved t test or Mann Whitney U test for continuous variables and chi-square for categorical variables with 2-sided p values to show significance.These tests were used to explore the relation between SVS and stroke subtypes,aiming at evaluating the diagnostic value of MRI-GRE.A 2-sided α level of 0.05 was used to show a statistically significant difference.Results:All patients with posterior circulation large artery occlusion from January 2003 to September 2013 were included.From January 2003 to September 2013,we identified 213 patients who had posterior circulation large artery occlusion,and 81 of them met the imaging eligibility criteria.In the 81 patients,21 of them had isolated brainstem infraction.Among the 21 members,SVS was detected in 7 patients(33%),and pseudo-SVS showed in 2 patients(10%).In the 7patients with SVS,we found atrial fibrillation in 2 patients,dissection in 3 patients and LAAD in 2 patients.There were SVS in 100% of patients with atrial fibrillation,50% of patients with dissection,20% of patients with LAAD,25% of patients with pontine infraction and 44% of patients with medullary infraction.Conclusion:The SVS could reflect pathology of deoxidized red cells composition inpatients with isolated brainstem infraction,which may be useful to explore the different stroke mechanisms and therapy strategies.Purpose:Acute ischemic stroke(IS)is a leading cause of death,disability,and dependence worldwide,making the identification of neuroprotective therapies vital.For decades,thrombolytic therapy with tissue plasminogen activator(t-PA),thrombectomy and anticoagulation may significantly improve patients’ clinical outcome after IS,however not all patients fit the criteria for t-PA therapy or thrombectomy,and the risk of hemorrhage after which is still increasing.Recently,researchers have paid more attention on the rehabilitation of neurological function after stroke,including the migration of neural stem cell,the tolerance of neurocyte under the situation of hypoxia and so on.In 2011,a randomized,placebo controlled trial,Fluoxetine for motor recovery after acute ischemic stroke(FLAME)demonstrated that Fluoxetine ameliorates the clinical outcome of patients with cerebral infraction,and may be the most promising drug in improving neurological function of patients after stroke.which may be closely related with hypoxia-inducible factor-1alpha(HIF-1α).In this study,we are aimed at exploring the influence of Fluoxetine to HIF-1α expression in SH-SY5 Y human neuroblastoma cells under hypoxia.Content:In this study,SH-SY5 Y cells were used as experimental materials to investigate the effect of Fluoxetine on the expression of HIF-1α under normal and hypoxia condition.We constructed the pc DNA3.0-HIF-1α plasmid and transfected into the cells to improve the concentration of HIF-1α,as HIF-1α was degenerated rapidly in normal condition.As for the hypoxia,cobalt chloride(Co Cl2)was utilized to simulate hypoxia condition,so as to establish a hypoxia cell model which had been treated with Fluoxetine in different concentrations and time.HIF-1α was concentrated by CO-Immunoprecipitation in order to explore the ubiquitination level of this protein.Methods:We established a SH-SY5 Y cell chemical hypoxia model by adding Co Cl2 into the culture medium in different concentration(0、100、200、300μmol/L)for different time length(0、2、6、12、24h).Then we treated SH-SY5 Y cells with Fluoxetine in different concentration(1、2、5μmol/L)and time length(0、2、6、10h).MTT and CCK-8 assay were used to detect the cell viability.Real-time PCR and western blot were used to measure the m RNA and protein level of HIF-1α.CO-Immunoprecipitation and western blot were used to measure the ubiquitination level of HIF-1α.Results:In normal condition,Fluoxetine has little influence on the expression of HIF-1α in SH-SY5 Y cells.SH-SY5 Y cell viability was gradually decreased as the increase of concentration and time length of Co Cl2,while 5μmol/L Fluoxetine did no harm to SH-SY5 Y cells.The protein level of HIF-1α was significantly increased with the increase of time length.200μmol/L Co Cl2 for 6h was quite suitable for inducing hypoxia.Fluoxetine(1、2、5μmol/L)could decrease the expression of HIF-1α significantly by enhance its ubiquitination under hypoxia for 6h,while with no obvious influence on the m RNA level of HIF-1α.The inhibition of HIF-1α caused by Fluoxetine was gradually decreased as time went on.Conclusion:Fluoxetine was able to influence the time of HIF-1α expression in SH-SY5 Y cell under hypoxia conditon,which was meaningful for the protection of neuro cells. |
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