Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood-brain barrier permeability after transient focal cerebral ischemia in mice

We have recently shown that melatonin decreases the late (24 hr) increase in blood-brain barrier (BBB) permeability and the risk of tissue plasminogen activator-induced hemorrhagic transformation following ischemic stroke in mice. In the study, we further explored whether melatonin would reduce postischemic neurovascular oxidative/nitrosative damage and, therefore, improve preservation of the early increase in the BBB permeability at 4 hr after transient focal cerebral ischemia for 60 min in mice. Melatonin (5 mg/kg) or vehicle was given intraperitoneally at the beginning of reperfusion. Hydroethidine (HEt) in situ detection and immunohistochemistry for nitrotyrosine were used to evaluate postischemic accumulation in reactive oxygen and nitrogen species, respectively, in the ischemic neurovascular unit. BBB permeability was evaluated by spectrophotometric and microscopic quantitation of Evans Blue leakage. Relative to controls, melatonin-treated animals not only had a significantly reduced superoxide accumulation in neurovascular units in boundary zones of infarction, by reducing 35% and 54% cytosolic oxidized HEt in intensity and cell-expressing percentage, respectively (P < 0.001), but also exhibited a reduction in nitrotyrosine by 52% (P < 0.01). Additionally, melatonin-treated animals had significantly reduced early postischemic disruption in the BBB permeability by 53% (P < 0.001). Thus, melatonin reduced postischemic oxidative/nitrosative damage to the ischemic neurovascular units and improved the preservation of BBB permeability at an early phase following transient focal cerebral ischemia in mice. The findings further highlight the ability of melatonin in anatomical and functional preservation for the ischemic neurovascular units and its relevant potential in the treatment of ischemic stroke.     

Melatonin reduces nitric oxide level during ischemia but not blood-brain barrier breakdown during reperfusion in a rat middle cerebral artery occlusion stroke model

Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that a single injection of melatonin before ischemia significantly reduced the infarct volume in both permanent and 3-hr middle cerebral artery occlusion (MCAO) rat stroke models. Nitric oxide (NO) and other free radicals play an important role in the pathogenesis of cerebral ischemia, and they have been postulated to mediate the breakdown of the blood-brain barrier (BBB) during ischemia. In this study, we evaluated the influence of melatonin, given at 30 min before MCAO, on brain NO concentration and BBB breakdown. Brain NO concentration was measured at 15 min of MCAO using electron paramagnetic resonance spectroscopy. BBB breakdown at 3 hr of reperfusion following 3 hr of MCAO was assessed using Evans blue extravasation. The relative brain NO concentration was increased to 141.69 +/- 9.71% (mean +/- S.E.M.; n = 9) at 15 min of MCAO. Treatment with melatonin at 1.5, 5, or 50 mg/kg significantly reduced the brain NO concentration to 104.20 +/- 11.20% (n = 8), 55.67 +/- 5.58% (n = 11), and 104.86 +/- 12.56% (n = 9), respectively. Melatonin at 5 mg/kg did not affect Evans blue extravasation. Our results suggest that a single injection of melatonin protects against focal cerebral ischemia partly via inhibition of ischemia-induced NO production and that this regimen does not prevent BBB breakdown following ischemia-reperfusion.     

Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats

We have previously shown that melatonin reduces postischemic rises in the blood-brain barrier (BBB) permeability and improves neurovascular dysfunction and hemorrhagic transformation following ischemic stroke. It is known that activation of the matrix metalloproteinases (MMPs) plays a crucial role in the pathogenesis of brain edema and hemorrhagic transformation after ischemic stroke. We, herein, investigated whether melatonin would ameliorate MMP-2 and MMP-9 activation and expression in a rat model of transient focal cerebral ischemia. Adult male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery (MCA) occlusion using an intraluminal filament. Melatonin (5 mg/kg) or vehicle was intravenously injected upon reperfusion. Brain infarction and hemorrhage within infarcts were measured, and neurological deficits were scored. The activity and expression of MMP-2 and MMP-9 were determined by zymography, in situ zymography and Western immunoblot analysis. Cerebral ischemia-reperfusion induced increased pro-MMP-9 and MMP-9 activity and expression 24 hr after reperfusion onset. Relative to controls, melatonin-treated animals, however, had significantly reduced levels in the MMP-9 activity and expression (P < 0.01), in addition to reduced brain infarct volume and hemorrhagic transformation as well as improved sensorimotor neurobehavioral outcomes. No significant change in MMP-2 activity was observed throughout the course experiments. Our results indicate that the melatonin-mediated reductions in ischemic brain damage and reperfusion-induced hemorrhage are partly attributed to its ability to reduce postischemic MMP-9 activation and increased expression, and further support the fact that melatonin is a suitable as an add-on to thrombolytic therapy for ischemic stroke patients.     

阿加曲班治疗急性缺血性脑卒中疗效及应用时机的临床研究

目的观察急性缺血性脑卒中后不同时间段应用阿加曲班的临床疗效。方法随机选取我院发病24h内的急性缺血性脑卒中患者80例,根据发病6～12h和13～24h 2个时间段应用阿加曲班,将患者分为A组28例,B组52例。7d后进行美国国立卫生研究院脑卒中量表(NIHSS)评分,以判定临床疗效。结果与治疗前比较,2组治疗后NIHSS评分明显降低,差异有统计学意义(P<0.05)。2组临床疗效比较差异无统计学意义(P>0.05)。结论阿加曲班治疗急性缺血性脑卒中有临床疗效。发病24h内不同时间应用对临床疗效无影响。     

Melatonin reduces disseminate neuronal death after mild focal ischemia in mice via inhibition of caspase-3 and is suitable as an add-on treatment to tissue-plasminogen activator

The effects of i.p. melatonin (4 + 4 mg/kg, after induction of ischemia and at reperfusion onset) administered either alone or in combination with the thrombolytic tissue-plasminogen activator (t-PA, 10 mg/kg), on cerebral laser Doppler flow (LDF) and ischemic injury were studied after 30 min of middle cerebral artery (MCA) thread occlusion in male C57BL/6 mice. Thread occlusions resulted in reproducible focal ischemias, followed by hyperperfusion reactions immediately after thread withdrawal, as revealed by LDF measurements. Compared with animals receiving normal saline (peak LDF after reperfusion: 172.0 +/- 24.2%), postischemic LDF was significantly attenuated in animals treated with melatonin (105.1 +/- 6.7%, P < 0.05). Delivery of t-PA (132.8 +/- 22.3%) or t-PA plus melatonin (164.7 +/- 36.7%), on the contrary, did not influence postischemic LDF recordings. Twenty-four hours after reperfusion, melatonin treated mice had significantly increased neuronal survival and decreased disseminate cell injury in the ischemia-vulnerable striatum, as investigated by cresyl violet and terminal transferase biotinylated-dUTP nick end labeling stainings. The protective effects were associated with inhibition of caspase-3 activity. Melatonin administration also increased neuronal survival after 30 min MCA occlusion in animals treated with t-PA, although t-PA itself already decreased the degree of injury in a significant manner. Our data demonstrate that melatonin reduces disseminated neuronal injury in the striatum after mild focal ischemia. Brain protection is independent of hemodynamic changes and involves inhibition of caspase-3.     

Melatonin attenuates gray and white matter damage in a mouse model of transient focal cerebral ischemia

We have previously shown that melatonin reduces infarct volumes and enhances neurobehavioral and electrophysiological recoveries following transient middle cerebral artery (MCA) occlusion in rats. In the study, we examined whether melatonin would display neuroprotection against neuronal, axonal and oligodendrocyte pathology after 24 hr of reperfusion following 1 hr of MCA occlusion in mice. Melatonin (5 mg/kg) or vehicle was given intraperitoneally at the commencement of reperfusion. Neurological deficits were assessed 24 hr after ischemia. Gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein and microtubule-associated protein tau-1 immunohistochemistry to identify postischemic disrupted axonal flow and oligodendrocyte pathology, respectively. Oxidative damage was assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) immunohistochemistry. Relative to controls, melatonin-treated animals not only had a significantly reduced volume of gray matter infarction by 42% (P<0.001), but also exhibited a decreased score of axonal damage by 42% (P<0.001) and a reduction in the volume of oligodendrocyte pathology by 58% (P<0.005). Melatonin-treated animals also had significantly reduced immunopositive reactions for 8-OHdG and 4-HNE by 53% (P<0.001) and 49% (P<0.001), respectively. In addition, melatonin improved sensory and motor neurobehavioral outcomes by 47 and 30%, respectively (P<0.01). Thus, delayed (1 hr) treatment with melatonin reduced both gray and white matter damage and improved neurobehavioral outcomes following transient focal cerebral ischemia in mice. The finding of reduced oxidative damage observed with melatonin suggests that its major mechanisms of action are mediated through its antioxidant and radical scavenging activity.     

缺血性脑血管病纤溶活性和血清同型半胱氨酸含量测定的临床意义

目的　探讨缺血性脑血管病 (ICVD)患者血浆纤溶活性和血清同型半胱氨酸 (Hcy)含量的变化及其临床意义。方法　入选ICVD患者 86例 (ICVD组 ) ,根据病情又分为短暂脑缺血发作 (TIA)组 14例 ,脑梗死组 72例 ,并入选非脑血管病患者 4 3例作为对照组 ,分别采用产色法测定血浆纤溶酶原 (Plg)、组织型纤溶酶原激活物 (t PA)、纤溶酶原激活抑制物 1(PAI 1)活性 ,荧光偏振光法测定血清Hcy,电化学发光法测定叶酸 ,同时常规测定血脂水平。结果　ICVD组 ,TIA患者和脑梗死患者血浆Plg、t PA活性均较对照组显著降低 (P <0 .0 5 )。ICVD组血清Hcy水平较对照组明显升高 (P <0 .0 1) ,t PA活性降低和高Hcy对ICVD的发生均有显著作用。结论　t PA活性降低和高Hcy分别是ICVD的独立危险因素     

阿替普酶静脉溶栓前应用依达拉奉对老年急性脑梗死预后的影响

目的 探讨老年急性脑梗死病人在应用阿替普酶(recombinant tissue plasminogen activator,rt-PA)静脉溶栓前预先使用依达拉奉的有效性和安全性.方法 采用回顾性分析的方法,纳入2014～2018年南京医科大学第二附属医院脑卒中登记系统中接受rt-PA静脉溶栓及依达拉奉联合治疗的老年...     

中重度脑白质疏松与急性脑梗死患者出血转化和预后关系的随访研究

目的探讨中重度脑白质疏松(leukoaraiosis,LA)对急性脑梗死患者出血转化和预后的影响。方法选取2015年6月至2018年5月浙江中医药大学附属第二医院神经内科收治的287例急性前循环脑梗死患者为研究对象,随访90 d。采用CT检查判断是否颅内出血,90 d mRS评价患者预后。依据Fazekas量表分为LA组和无LA组,比较两组患者的临床特征,并用Logistic回归分析LA对急性脑梗死患者出血转化和预后的影响。结果急性前循环脑梗死合并LA者91例(31.7%),出血转化发生率为20.9%(19/91),预后不良为46.2%(42/91);无LA的急性前循环脑梗死者196例(68.3%),出血转化发生率为11.7%(23/196),预后不良为20.4%(40/196)。出血转化危险因素Logistic回归分析显示:中重度LA是急性前循环脑梗死患者出血转化的独立危险因素(回归系数=0.765,标准误=0.275,Wald值=7.739,OR=2.149,95%CI:1.254~3.684,P=0.012)。90 d预后危险因素Logistic回归分析显示:中重度LA是急性前循环脑梗死患者预后不良的独立危险因素(回归系数=0.848,标准误=0.357,Wald值=5.642,OR=2.335,95%CI:1.160~4.701,P=0.031)。结论合并中重度LA的急性前循环脑梗死患者发生出血转化的比例高,90 d预后差,且中重度LA是急性前循环脑梗死出血转化和预后不良的独立危险因素。     

Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice

Cyclooxygenase (COX)-2 plays a harmful role in cerebral ischemic/reperfusion injury, but the role of COX-1 is uncertain. In the present study, cerebral infarct was induced by photothrombosis. Intraperitoneal injections of melatonin at 15 g/kg or its vehicle were made at 0.5 hr before stroke and 24 and 48 hr after stroke. Cerebral blood flow (CBF) in the penumbra was monitored during stroke using a laser Doppler flowmeter. Sensorimotor behavior was evaluated using the turning in an alley and falling from a pole tests at 1 hr before stroke and 24 and 48 hr after stroke. Infarct volume was determined from the T2-weighted magnetic resonance images at 72 hr after stroke. During the first 15 min of stroke, CBF decreased in the penumbra in both homozygous COX-1-gene knockout and wild-type mice. Melatonin treatment improved the penumbral CBF in the wild-type mice. Mild poststroke impairment in sensorimotor behavior was detected by the turning in an alley test in which the COX-1-gene knockout mice performed better. Melatonin treatment did not affect the poststroke sensorimotor behavior. The relative infarct volume at 72 hr after stroke was 8.1% and 8.4% in the COX-1-gene knockout and wild-type mice, respectively. Melatonin treatment reduced the relative infarct volume to 6.3% in the latter but not in the former (8.2%). Thus, COX-1-gene knockout does not affect the brain's susceptibility to photothrombotic stroke. Melatonin treatment reduces infarct size in the wild-type mice following photothrombotic stroke partly via maintenance of penumbral CBF in which the COX-1-gene may play a role.     

高龄脑梗死患者重组组织型纤溶酶原激活剂静脉溶栓的有效性和安全性

目的探讨高龄脑梗死患者应用重组组织型纤溶酶原激活剂(rt -PA)静脉溶栓治疗的有效性和安全性。方法选择急性脑梗死患者196例,根据患者年龄分为<80岁组141例和≥80岁组55例,发病<4.5 h的患者给予rt-PA静脉溶栓治疗,比较2组患者溶栓前、溶栓后14 d的美国国立卫生研究院卒中量表(NIHSS)评分,观察溶栓后颅内出血(ICH)和症状性颅内出血(sICH)的发生率。90 d随访时,采用改良Rankin's评分评定临床结局。结果 2组溶栓后14 d的NIHSS评分都较溶栓前显著降低(P<0.01),<80岁组较≥80岁组NIHSS评分降低更明显(P<0.01)。≥80岁组的病死率显著高于<80岁组(P<0.05);<80岁组和≥80岁组预后良好的比例分别为57.5%和45.5%(P>0.05),ICH发生率分别为16.3%和21.8%,sICH发生率分别为6.4%和14.5%(P>0.05)。结论高龄脑梗死患者应用rt-PA静脉溶栓和年龄<80岁者同样是安全有效的。     

估算的肾小球滤过率、血尿酸和纤维蛋白原与缺血性脑卒中溶栓后脑出血转化的关系及对结局的预测价值

目的探讨估算的肾小球滤过率(eGFR)、血尿酸(SUA)、纤维蛋白原(FIB)与缺血性脑卒中溶栓后脑出血转化及临床结局的关系。方法选取158例缺血性脑卒中用重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓患者,包括无脑出血转化121例、脑出血转化37例。采用Logistic回归方程分析rt-PA静脉溶栓后脑出血转化影响因素;对比不同早期神经功能患者eGFR、SUA、FIB水平;评价eGFR、SUA、FIB对早期神经功能恶化(END)的预测价值;比较不同eGFR、SUA、FIB水平患者的累积生存率。结果rt-PA静脉溶栓2 h、24 h后,脑出血转化者eGFR、SUA、FIB水平较无脑出血转化者降低(P<0.05)。Logistic回归分析显示,年龄、基线NIHSS评分、基线舒张压、大面积脑梗死及溶栓后2 h和24 h的eGFR、SUA、FIB均为rt-PA静脉溶栓后脑出血转化的影响因素(P<0.05)。END患者溶栓后2 h和24 h的eGFR、SUA、FIB均低于非END患者(P<0.05)。ROC曲线分析显示,溶栓后24 h的eGFR、SUA、FIB联合预测END的曲线下面积为0.809,大于任一单一指标,其灵敏度、特异度分别为80.95%、74.14%。生存分析结果表明,溶栓后24 h的eGFR、SUA、FIB高水平组的累积生存率高于低水平组(P<0.05)。结论eGFR、SUA、FIB与缺血性脑卒中预后密切相关,监测上述指标有助于脑出血转化诊断及END预测。     

早期血脑屏障损伤在急性缺血性卒中 tP A溶栓后出血性转化中的作用及其机制

出血性转化（hemorrhagictransformation,HT）是急性缺血性卒中患者组织型纤溶酶原激活剂（tissue type plasminogen activator, tPA）溶栓治疗后最严重的并发症,极大地限制了tPA的临床应用。早期血脑屏障（blood brain barrier, BBB）损伤可能是发生HT 的重要机制,维持BBB完整性可显著降低HT 风险。文章就早期BBB损伤在tPA溶栓后HT中的作用、机制和预防措施进行了综述。     

脑缺血预处理对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9表达的影响

目的 探讨脑缺血预处理(ischemic preconditioning,IP)对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响.方法 154只Wistar大鼠随机分为假手术组(14只)、非缺血预处理(non-ischemic preconditioning,NIP)组(70只)和IP组(70只),后两组再随机分为5个亚组,每组14只.线栓法建立大脑中动脉闭塞模型,缺血预处理10 min,分别在IP后1、3、7、14和21 d进行再次缺血2 h再灌注22 h.采用2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色测定脑梗死体积,通过测定渗出血管外的伊文思蓝(Evans blue,EB)含量评价血脑屏障通透性,采用于湿重法评价脑水肿程度,免疫组化染色和原位杂交法检测MMP-9蛋白和mRNA表达.结果 与NIP组相应亚组比较,IP组缺血预处理1、3和7 d亚组神经功能缺损评分显著降低,脑梗死体积显著缩小,EB含量和脑水含量显著降低,MMP-9蛋白和mRNA表达均显著下调(P＜0.05或P＜0.01).IP组1、3和7 d亚组梗死体积和MMP-9 mRNA表达较IP组14 d和21 d亚组显著缩小或下调,3 d和7 d亚组EB含量、脑水含量和MMP-9蛋白表达较其他亚组显著降低,其中以3 d亚组降低最显著(P＜0.05).结论 缺血预处理诱导的血脑屏障通透性改变和MMP-9表达下调在脑缺血耐受中发挥着重要作用.     

Clinical safety and outcome of recombinant tissue plasminogen activator in patients with stroke attributable to small artery occlusion: A protocol for systematic review and meta-analysis

Background:Recent observations raised concern that the intravenous recombinant tissue plasminogen activator (rt-PA) may result in damage to stroke patients caused by small artery occlusion (SAO). Thus, we perform a protocol for meta-analysis to investigate the efficacy and safety of intravenous thrombolysis with rt-PA in SAO-patients.Methods:The search-style electronic libraries, including Pubmed, Embase, the Cochrane Library, Web of Science, Wanfang Data, VIP Chinese Journals, and China Biomedical Literature Service System are used for document retrieval in June 2021 with no restrictions on language. The risk of bias in include articles will be assessed using the Cochrane Risk of Bias Tool. We perform the meta-analysis by Stata version 10.0 software and calculated the statistics using the inverse variance statistical method. Binary outcomes are presented as Mantel-Haenszel-style risk ratios with 95% confidence interval. Continuous outcomes are reported as mean differences.Results:The results of the article will be shown in a peer-reviewed journal.Conclusion:Intravenous rt-PA may be effective and safe in SAO-patients.     

尿激酶和巴曲酶治疗早期急性脑梗死的疗效和安全性研究

目的比较尿激酶和巴曲酶治疗超早期脑梗死的效果和安全性。方法比较150万单剂量尿激酶和不同剂量及给药时间的巴曲酶治疗发病6 h内脑梗死的效果。以治疗后3个月和6个月死亡率、改良Rankin评分(mRS)和巴塞尔指数(BI)作为主要终结指标,以美国国家卫生研究所卒中评分(NIHSS)变化作为次要终结指标,收录患者74例。分为A组(尿激酶组)26例,B组(巴曲酶常规剂量组)25例,C组(巴曲酶加大剂量及延长疗程组)23例。结果尿激酶和巴曲酶均可以改善部分患者神经功能评分,2h内尿激酶平均改善NIHSS较快,但是有波动,而巴曲酶效果较平缓而稳定。3个月时A、B、C各组的BI 95~100分患者占的比例分别是26.9%,33.3%,28.6%;mRS 0~2分患者分别为42.3%,41.7%,42.9%;6个月BI 95~100分患者占的比例分别是50.0%,58.3%,47.6%;mRS 0~2分患者分别为57.7%,66.7%,57.1%。差异均无显著性意义。结论缺血性脑卒中6 h内给予尿激酶或者巴曲酶对3个月和6个月后终结指标影响没有显著差异。     

Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats

We have previously shown that exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia-reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. Melatonin (5 mg/kg) or vehicle was given intravenously at reperfusion onset. Immunohistochemistry and flow cytometric analysis were used to evaluate the cellular inflammatory response at 48 hr after reperfusion. Relative to controls, melatonin-treated animals did not have significantly changed systemic cellular inflammatory responses in the bloodstream (P > 0.05). Melatonin, however, significantly decreased the cellular inflammatory response by 41% (P < 0.001) in the ischemic hemisphere. Specifically, melatonin effectively decreased the extent of neutrophil emigration (Ly6G-positive/CD45-positive) and macrophage/activated microglial infiltration (CD11b-positive/CD45-positive) by 51% (P < 0.01) and 66% (P < 0.01), respectively, but did not significantly alter the population composition of T lymphocyte (CD3-positive/CD45-positive; P > 0.05). This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients.     

Anticoagulant management by low-dose of low molecular weight heparin in patients with nonvalvular atrial fibrillation following hemorrhagic transformation and complicated with venous thrombosis: Five case reports and literature review

For patients with nonvalvular atrial fibrillation (NVAF) following hemorrhagic infarction (HI)/hemorrhage transformation (HT) and complicated with venous thrombosis, the management of anticoagulation is controversial. Our study intends to explore the safety and effectiveness of using low-dose of low molecular weight heparin (LMWH) to treat NVAF patients with HI (or HT) and complicated with venous thrombosis.Between January 2018 and January 2019, NVAF related acute ischemic stroke patients with HT/HI, hospitalized in the department of neurology or rehabilitation in our hospital, are enrolled retrospectively. Among them, those who were found to have venous thrombosis and undergo anticoagulation (LMWH) during the treatment were extracted. We investigate the efficacy and safety in those patients who have been treated with anticoagulant of LMWH.Five cases accepted LMWH within 3 weeks attributed to the appearance of venous thrombosis, and all of them did not display new symptomatic bleeding or recurrent stroke. However, based on the results of a head computed tomography scan, there were 2 cases of slightly increased intracranial hemorrhage, and then we reduced the dose of anticoagulant. In addition, color ultrasound showed that venous thrombosis disappeared or became stable.Patients with NVAF following HI/HT have a higher risk of thromboembolism. Early acceptance of low-dose LMWH as an anticoagulant is relatively safe and may gain benefit. However, in the process of anticoagulant therapy, we should follow-up head computed tomography/magnetic resonance imaging frequently, as well as D-dimer values, limb vascular ultrasound. Besides, the changes of symptoms and signs should be focused to judge the symptomatic bleeding or recurrent stroke. Furthermore, it is better to adjust anticoagulant drug dosage according to specific conditions.