| Background and Purpose: Several studies have demonstrated that fluoxetine can improve clinical outcome in patients with cerebral infarction,particularly promote motor function recovery.Hypoxia inducible factor-1α(HIF-1α)is a major cytokine that regulate the expression of downstream gene under hypoxia.Our previous studies showed that fluoxetine induces VEGF/Netrin overexpression via the mediation of HIF-1α.Based on this,we hypothesize that fluoxetine may promote angiogenesis and provide neuroprotection through the HIF-1α-VEGF/Netrin pathway in a rat model of transient cerebral ischemia.Materials and Methods: The transient middle cerebral artery occlusion model(t MCAO)was established in Sprague-Dawley(SD)rats.The SD rats were divided into a t MCAO + fluoxetine group,a t MCAO + saline group and a sham operation +Saline group.Fluoxetine(20mg/kg/d)or equal dose of saline were given by oral gavage for 4 weeks 24 hours after the operations.The behavioral test and infarct volume measurement were performed(1,2,3,and 4 week)after the operation.Next,the expression of HIF-1α,Netrin,VEGF and apoptosis protein were examined by western blotting at 1,2 and 4 week,respectively after t MCAO.Synchrotron radiation was used to observe the microangiography of brain in the fourth week..Results: In week 3 and 4,the ladder test and the balance beam test in the t MCAO +fluoxetine group were significantly improved compared with t MCAO + saline group(P <0.05).No significant difference in infarct volume was found in week 1,2 and 3,but infarct volume in the t MCAO + fluoxetine group decreased significantly in the fourth week compared with t MCAO + saline group(P <0.05).In week 1 to week 4after t MCAO,HIF-1α expression was significantly up-regulated in the t MCAO +fluoxetine group compared with other groups.Accordlingly,the levels of Netrin and its receptor DCC,VEGF and its receptor VEGFR were significantly increased in 1,2,3 and 4 week.The expression of Bax,Bad were reduced,and Bcl-2,Bcl-x L were increased in the fourth week.The percentage of apoptosis cell was significantly reduced in the t MCAO + fluoxetine group.Synchrotron radiation and microvascular staining at week 4 showed increased neovascularization in the t MCAO + fluoxetine group.Conclusion: In the rat model of t MCAO,Fluoxetine improves the motor function and decreases infarct volume through the promotion of angiogenesis and neuroprotection by up-regulating the expression of HIF-1α-Netrin/VEGF pathway and inhibiting apoptosis.Purpose: Alberta Stroke Program Early Computed Tomography(CT)score(ASPECTS)has been applied to MRI diffusion weighted imaging(DWI)with good interrater agreement to predict early ischemic stroke,and it can be useful in decision making in acute ischemic stroke.This study aims to assess the value of MRI DWI ASPECTS to predict hemorrhagic transformation(HT)in acute cardioembolic stroke.Methods: This is a single-enter,retrospective study with 52 patients with acute cardioembolic stroke enrolled from January 2008 to September 2013.Baseline non-contrast CT(NCCT)were done within 12 hour after index stroke.MRI scan was performed within 72 h of symptom onset including MRI DWI,T2*-weighted gradient echo to identify HT.NCCT and DWI ASPECTS were measured by a neurologist and a neuroradiologist.Results: Among the 52 patients,eighteen(34.6%)patients had HT and four(7.7%)developed symptomatic HT.On the univariate analysis,the DWI-ASPECTS of patients with HT was significantly less than patients without HT(6±2 vs 7±2,P = 0.005),and the proportion of patients with DWI-ASPECTS 0–7 was significantly higher in HT patients as compared to patients without HT(16//18,89%vs 16/34,47%,P = 0.008).The multivariate analysis showed that DWI-ASPECTS 0–7 was still associated with the HT significantly [OR 13.23(95%CI 2.20-79.48,P = 0.005)]。.Conclusion: MRI DWI-ASPECTS could be of value to predict HT risk after acute cardioembolic stroke. |
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