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Oestrogen ameliorates blood-brain barrier damage after experimental subarachnoid haemorrhage via the SHH pathway in male rats. 雌性激素通过SHH通路改善雄性大鼠实验性蛛网膜下腔出血后血脑屏障损伤。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-06-01 DOI: 10.1136/svn-2022-001907
Jie Zhang, Haiying Li, Zhongmou Xu, Jinxin Lu, Chang Cao, Haitao Shen, Xiang Li, Wanchun You, Gang Chen

Background: Sex differences affect the occurrence, progression and regression of subarachnoid haemorrhage (SAH). Oestrogen plays a protective role in alleviating the vasospasm and neuronal apoptosis induced by SAH. However, whether oestrogen affects blood‒brain barrier (BBB) integrity has not been fully studied. Oestrogen has been found to regulate the sonic hedgehog (SHH) signalling pathway through the oestrogen receptor in gastric cancer and adrenal glands, and the SHH signalling pathway has an important role in maintaining the BBB by upregulating the expression of tight junction proteins. In this study, we investigated the relationship between oestrogen and the SHH signalling pathway using clinical data and established an experimental SAH model to explore whether oestrogen could ameliorate BBB damage after SAH through the SHH pathway.

Methods: Correlations between oestrogen and the SHH pathway were analysed by patients' cerebrospinal fluid (CSF) samples and the Genotype-Tissue Expression database (GTEx). Then, an experimental rat SAH model was established using the endovascular perforation method and treated with oestrogen, oestrogen inhibitors and SHH signalling pathway inhibitors. Then, the effects of oestrogen on BBB damage were analysed by western blot, immunofluorescence and neurobehavioural experiments.

Results: ESLIA detection and correlation analysis showed that oestrogen levels in patients' CSF were positively correlated with the SHH pathway, which was further verified by GTEx gene-correlation analysis. SHH was found to be mainly expressed in neurons and astrocytes in rats under physiological conditions and was upregulated by oestrogen pretreatment. In the SAH model, oestrogen pretreatment was found to reverse SAH-induced decreases in the SHH pathway, which were counteracted by oestrogen receptor inhibitors. Furthermore, oestrogen pretreatment reduced SAH-induced BBB damage, brain oedema and neurological dysfunction, which were eliminated by SHH pathway inhibitors.

Conclusion: In conclusion, we demonstrate here that oestrogen pretreatment ameliorates brain injury after SAH, at least in part through SHH pathway-mediated BBB protection.

背景:性别差异影响蛛网膜下腔出血(SAH)的发生、进展和消退。雌激素在减轻SAH引起的血管痉挛和神经元凋亡中起保护作用。然而,雌激素是否影响血脑屏障(BBB)完整性尚未得到充分研究。在胃癌和肾上腺中已发现雌激素通过雌激素受体调控sonic hedgehog (SHH)信号通路,SHH信号通路通过上调紧密连接蛋白的表达在血脑屏障的维持中起重要作用。在本研究中,我们利用临床数据研究了雌激素与SHH信号通路的关系,并建立了实验性SAH模型,探讨雌激素是否可以通过SHH通路改善SAH后血脑屏障损伤。方法:通过患者脑脊液(CSF)样本和基因型组织表达数据库(GTEx)分析雌激素与SHH通路的相关性。然后,采用血管内穿孔法建立实验性大鼠SAH模型,并用雌激素、雌激素抑制剂和SHH信号通路抑制剂治疗。采用western blot、免疫荧光和神经行为实验分析雌激素对血脑屏障损伤的影响。结果:ESLIA检测及相关分析显示,患者脑脊液雌激素水平与SHH通路呈正相关,GTEx基因相关分析进一步证实了这一点。生理条件下,SHH主要在大鼠的神经元和星形胶质细胞中表达,并通过雌激素预处理上调。在SAH模型中,雌激素预处理被发现可以逆转SAH诱导的SHH通路的减少,这种减少可以被雌激素受体抑制剂抵消。此外,雌激素预处理可减少SHH通路抑制剂可消除的sah诱导的血脑屏障损伤、脑水肿和神经功能障碍。结论:总之,我们在这里证明了雌激素预处理可以改善SAH后的脑损伤,至少部分是通过SHH通路介导的血脑屏障保护。
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引用次数: 2
Endovascular therapy in acute anterior circulation large vessel occlusive patients with a large infarct core (ANGEL-ASPECT): protocol of a multicentre randomised trial. 血管内治疗急性前循环大血管闭塞伴大梗死核心患者(ANGEL-ASPECT):一项多中心随机试验方案。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001865
Xiaochuan Huo, Gaoting Ma, Xuelei Zhang, Yuesong Pan, Xu Tong, Dapeng Sun, Liping Liu, Yilong Wang, David S Liebeskind, Yongjun Wang, Vitor Mendes Pereira, Zeguang Ren, Zhongrong Miao

Background: The benefit of stroke thrombectomy for large infarct core still lacks robust randomised controlled studies.

Aim: To demonstrate the design of a clinical trial on endovascular therapy for acute anterior circulation large vessel occlusion (LVO) patients with large infarct core volume.

Design: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100 mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well.

Study outcomes: The primary efficacy outcome is 90 (±7) days modified Rankin Scale. Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome.

Discussion: The ANGEL-ASPECT trial will screen patients with large infarct core (ASPECTS 3-5 or 70-100 mL) through image evaluation criteria within 24 hours and explore the efficacy and safety of endovascular therapy compared with BMM.

背景:卒中血栓切除术治疗大面积梗死核心的益处仍然缺乏可靠的随机对照研究。目的:探讨血管内治疗急性前循环大血管闭塞(LVO)大梗死核容量患者的临床试验设计。设计:ANGEL-ASPECT是一项多中心、前瞻性、随机、开放标签、盲法终点试验,旨在评估与BMM单独治疗相比,最佳医疗管理(BMM)联合血管内治疗是否能改善阿尔伯塔卒中急性LVO患者的神经功能结局,这些患者在非对比CT上的早期CT评分(ASPECTS)为3-5或梗死核心体积范围为70- 100ml(定义为rCBF)。研究结果:主要疗效结局为90(±7)天修改后的Rankin量表。随机分组后48小时内出现症状性颅内出血是主要的安全结局。讨论:ANGEL-ASPECT试验将在24小时内通过图像评价标准筛选大梗死核心(ASPECTS 3-5或70-100 mL)患者,并与BMM比较探讨血管内治疗的有效性和安全性。
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引用次数: 4
Low LDL-C level and intracranial haemorrhage risk after ischaemic stroke: a prospective cohort study. 低LDL-C水平与缺血性脑卒中后颅内出血风险:一项前瞻性队列研究
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001612
Jie Xu, Zimo Chen, Meng Wang, Jinglin Mo, Jing Jing, Gulbahram Yalkun, Liye Dai, Xia Meng, Hao Li, Zixiao Li, Yongjun Wang

Background and purpose: The Treat Stroke to Target trial has confirmed the benefit of targeting low-density lipoprotein cholesterol (LDL-C) of <1.8 mmol/L in patients who had an ischaemic stroke (IS). However, haemorrhagic risk brought by this target level (<1.8 mmol/L) or even lower level (<1.4 mmol/L) of LDL-C should also be concerned. In this study, we aimed to demonstrate whether low LDL-C could increase the intracranial haemorrhage risk following IS.

Methods: Patients who had an IS from China Stroke Center Alliance programme with complete baseline information were prospectively enrolled. 793 572 patients who had an IS were categorised into 6 groups according to LDL-C level (<1.40 mmol/L, 1.40-1.79 mmol/L, 1.80-2.59 mmol/L, 2.60-2.99 mmol/L, 3.00-4.89 mmol/L, ≥4.90 mmol/L). The study outcome was defined as intracranial haemorrhage identified during hospitalisation. Logistic regression model was used to examine the association between different LDL-C levels and risk of intracranial haemorrhage.

Results: Compared with patients of LDL-C=1.80-2.59 mmol/L, both subgroups of LDL-C<1.40 mmol/L and LDL-C=1.40-1.79 mmol/L showed significantly higher risk of intracranial haemorrhage (OR=1.26, 95% CI=1.18 to 1.35; OR=1.22, 95% CI=1.14 to 1.30, respectively). Interaction effect was found to exist between the subgroups of intravenous thrombolytic therapy (p=0.04), rather than the subgroups of age, sex and body mass index. Moreover, the sensitivity analyses indicated that even patients who had an IS with minor stroke still suffered from the increased intracranial haemorrhage risk related to low LDL-C level.

Conclusions: Among patients who had an IS, the low LDL-C level (<1.4 mmol/L or <1.8 mmol/L) at baseline is associated with increased risk of intracranial haemorrhage during acute stage. While actively lowering LDL-C level for patients who had an IS, clinicians should also concern about the haemorrhagic risk associated with low LDL-C level.

背景和目的:卒中靶向治疗试验证实了靶向治疗低密度脂蛋白胆固醇(LDL-C)的益处。方法:前瞻性纳入来自中国卒中中心联盟项目的具有完整基线信息的IS患者。将793 572例IS患者根据LDL-C水平分为6组(结果:与LDL-C=1.80 ~ 2.59 mmol/L的患者相比,两个亚组LDL-C水平均较低)。
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引用次数: 0
Associations of HDL-C/LDL-C with myocardial infarction, all-cause mortality, haemorrhagic stroke and ischaemic stroke: a longitudinal study based on 384 093 participants from the UK Biobank. HDL-C/LDL-C与心肌梗死、全因死亡率、出血性卒中和缺血性卒中的关系:一项基于英国生物银行384 093名参与者的纵向研究。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001668
Shiqi Yuan, Xiaxuan Huang, Wen Ma, Rui Yang, Fengshuo Xu, Didi Han, Tao Huang, MIn Peng, Anding Xu, Jun Lyu

Objective: To explore the correlations of high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C) with myocardial infarction (MI), all-cause mortality, haemorrhagic stroke and ischaemic stroke, as well as the joint association of genetic susceptibility and HDL-C/LDL-C with the MI risk.

Methods and results: This study selected 384 093 participants from the UK Biobank (UKB) database. First, restricted cubic splines indicated non-linear associations of HDL-C/LDL-C with MI, ischaemic stroke and all-cause mortality. Second, a Cox proportional-hazards model indicated that compared with HDL-C/LDL-C=0.4-0.6, HDL-C/LDL-C<0.4 and >0.6 were correlated with all-cause mortality (HR=0.97 for HDL-C/LDL-C<0.4, 95% CI=0.939 to 0.999, p<0.05; HR=1.21 for HDL-C/LDL-C>0.6, 95% CI=1.16 to 1.26, p<0.001) after full multivariable adjustment. HDL-C/LDL-C<0.4 was correlated with a higher MI risk (HR=1.36, 95% CI=1.28 to 1.44, p<0.05) and ischaemic stroke (HR=1.12, 95% CI=1.02 to 1.22, p<0.05) after full multivariable adjustment. HDL-C/LDL-C>0.6 was associated with higher risk haemorrhagic stroke risk after full multivariable adjustment (HR=1.25, 95% CI=1.03 to 1.52, p<0.05). Third, after calculating the coronary heart disease Genetic Risk Score (CHD-GRS) of each participant, the Cox proportional-hazards model indicated that compared with low CHD-GRS and HDL-C/LDL-C=0.4-0.6, participants with a combination of high CHD-GRS and HDL-C/LDL-C<0.4 were associated with the highest MI risk (HR=2.45, 95% CI=2.15 to 2.8, p<0.001). Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS.

Conclusion: In UKB participants, HDL-C/LDL-C ratio of 0.4-0.6 was correlated with lower MI risk, all-cause mortality, haemorrhagic stroke and ischaemic stroke. Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS. The clinical significance and impact of HDL-C/LDL-C need to be further verified in future studies.

目的:探讨高密度脂蛋白胆固醇(HDL-C)/低密度脂蛋白胆固醇(LDL-C)与心肌梗死(MI)、全因死亡率、出血性卒中和缺血性卒中的相关性,以及遗传易感性和HDL-C/LDL-C与MI风险的联合关系。方法和结果:本研究从UK Biobank (UKB)数据库中选择384093名参与者。首先,受限三次样条曲线表明HDL-C/LDL-C与心肌梗死、缺血性卒中和全因死亡率呈非线性关联。其次,Cox比例风险模型显示,与HDL-C/LDL-C=0.4-0.6相比,HDL-C/LDL-C0.6与全因死亡率相关(HDL-C/LDL-C0.6的HR=0.97, 95% CI=1.16 ~ 1.26, p0.6与全多变量调整后的出血性卒中风险较高相关(HR=1.25, 95% CI=1.03 ~ 1.52, p0.6)。结论:在UKB参与者中,HDL-C/LDL-C比值0.4-0.6与较低的心肌梗死风险、全因死亡率、出血性卒中和缺血性卒中相关。HDL-C/LDL-C患者
{"title":"Associations of HDL-C/LDL-C with myocardial infarction, all-cause mortality, haemorrhagic stroke and ischaemic stroke: a longitudinal study based on 384 093 participants from the UK Biobank.","authors":"Shiqi Yuan,&nbsp;Xiaxuan Huang,&nbsp;Wen Ma,&nbsp;Rui Yang,&nbsp;Fengshuo Xu,&nbsp;Didi Han,&nbsp;Tao Huang,&nbsp;MIn Peng,&nbsp;Anding Xu,&nbsp;Jun Lyu","doi":"10.1136/svn-2022-001668","DOIUrl":"https://doi.org/10.1136/svn-2022-001668","url":null,"abstract":"<p><strong>Objective: </strong>To explore the correlations of high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C) with myocardial infarction (MI), all-cause mortality, haemorrhagic stroke and ischaemic stroke, as well as the joint association of genetic susceptibility and HDL-C/LDL-C with the MI risk.</p><p><strong>Methods and results: </strong>This study selected 384 093 participants from the UK Biobank (UKB) database. First, restricted cubic splines indicated non-linear associations of HDL-C/LDL-C with MI, ischaemic stroke and all-cause mortality. Second, a Cox proportional-hazards model indicated that compared with HDL-C/LDL-C=0.4-0.6, HDL-C/LDL-C<0.4 and >0.6 were correlated with all-cause mortality (HR=0.97 for HDL-C/LDL-C<0.4, 95% CI=0.939 to 0.999, p<0.05; HR=1.21 for HDL-C/LDL-C>0.6, 95% CI=1.16 to 1.26, p<0.001) after full multivariable adjustment. HDL-C/LDL-C<0.4 was correlated with a higher MI risk (HR=1.36, 95% CI=1.28 to 1.44, p<0.05) and ischaemic stroke (HR=1.12, 95% CI=1.02 to 1.22, p<0.05) after full multivariable adjustment. HDL-C/LDL-C>0.6 was associated with higher risk haemorrhagic stroke risk after full multivariable adjustment (HR=1.25, 95% CI=1.03 to 1.52, p<0.05). Third, after calculating the coronary heart disease Genetic Risk Score (CHD-GRS) of each participant, the Cox proportional-hazards model indicated that compared with low CHD-GRS and HDL-C/LDL-C=0.4-0.6, participants with a combination of high CHD-GRS and HDL-C/LDL-C<0.4 were associated with the highest MI risk (HR=2.45, 95% CI=2.15 to 2.8, p<0.001). Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS.</p><p><strong>Conclusion: </strong>In UKB participants, HDL-C/LDL-C ratio of 0.4-0.6 was correlated with lower MI risk, all-cause mortality, haemorrhagic stroke and ischaemic stroke. Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high, intermediate or low CHD-GRS. The clinical significance and impact of HDL-C/LDL-C need to be further verified in future studies.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/6f/svn-2022-001668.PMC10176979.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9917807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850). 西洛他唑和单硝酸异山梨酯预防脑血管疾病进展:腔隙干预试验-2 (LACI-2) (ISRCTN14911850)的基线数据和统计分析计划。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001816
Philip M Bath, Iris Mhlanga, Lisa J Woodhouse, Fergus Doubal, Katherine Oatey, Alan A Montgomery, Joanna M Wardlaw

Background: Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD.

Methods: The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at 1 year after randomisation; and safety (bleeding, falls, death). Data are number (%) and median (IQR).

Results: The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 (56.0, 72.0) years, female 112 (30.9%), stroke onset to randomisation 79.0 (27.0, 244.0) days, hypertension 267 (73.6%), median blood pressures 143.0 (130.0, 157.0)/83.0 (75.0, 90.0) mm Hg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 (0.0, 1.0), National Institutes Health stroke scale 1.0 (1.4), Montreal Cognitive Assessment 26.0 (23.0, 28.0) and total SVD score on brain imaging 1.0 (0.0, 2.0). This publication summarises the baseline data and presents the statistical analysis plan.

Summary: The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.

Trial registration number: ISRCTN14911850.

背景:脑血管病(SVD)可导致腔隙性卒中(占所有缺血性卒中的25%)、身体虚弱和认知障碍以及血管性和混合性痴呆。没有特定的治疗方法来防止SVD的进展。方法:LACunar干预试验-2是一项由研究者发起的前瞻性随机开放标签盲终点II期可行性研究,评估西洛他唑和单硝酸异山梨酯预防SVD进展的可行性。我们的目的是招募400名临床明显的腔内缺血性卒中患者,并在部分因子设计中随机分配到西洛他唑,单硝酸异山梨酯,两者都使用或不使用,此外还有指导方针的继发性缺血性卒中预防。主要结局是招募的可行性和药物依从性;主要次要结局包括:药物耐受性;随机分组后1年血管事件复发、认知和功能;还有安全(流血、摔倒、死亡)。数据为数字(%)和中位数(IQR)。结果:该试验于2018年2月5日开始,并于2021年5月31日停止招募,随机分配了363例患者,具有以下基线特征:平均年龄64岁(56.0,72.0)岁,女性112岁(30.9%),卒中发作时间为79.0(27.0,244.0)天,高血压267(73.6%),中位血压143.0 (130.0,157.0)/83.0 (75.0,90.0)mm Hg,当前吸烟者67(18.5%),教育程度达到学校毕业考试(A-level)或更高118(32.5%),修改Rankin量表1.0(0.0,1.0),国立卫生研究院卒中量表1.0(1.4),蒙特利尔认知评估26.0(23.0,28.0)和脑成像SVD总分1.0 (0.0,1.0),2.0)。本出版物总结了基线数据并提出了统计分析计划。摘要:该试验目前正在进行后续工作,将于2022年5月31日完成,预计将于2022年10月取得结果。试验注册号:ISRCTN14911850。
{"title":"Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850).","authors":"Philip M Bath,&nbsp;Iris Mhlanga,&nbsp;Lisa J Woodhouse,&nbsp;Fergus Doubal,&nbsp;Katherine Oatey,&nbsp;Alan A Montgomery,&nbsp;Joanna M Wardlaw","doi":"10.1136/svn-2022-001816","DOIUrl":"https://doi.org/10.1136/svn-2022-001816","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD.</p><p><strong>Methods: </strong>The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at 1 year after randomisation; and safety (bleeding, falls, death). Data are number (%) and median (IQR).</p><p><strong>Results: </strong>The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 (56.0, 72.0) years, female 112 (30.9%), stroke onset to randomisation 79.0 (27.0, 244.0) days, hypertension 267 (73.6%), median blood pressures 143.0 (130.0, 157.0)/83.0 (75.0, 90.0) mm Hg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 (0.0, 1.0), National Institutes Health stroke scale 1.0 (1.4), Montreal Cognitive Assessment 26.0 (23.0, 28.0) and total SVD score on brain imaging 1.0 (0.0, 2.0). This publication summarises the baseline data and presents the statistical analysis plan.</p><p><strong>Summary: </strong>The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.</p><p><strong>Trial registration number: </strong>ISRCTN14911850.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6c/e8/svn-2022-001816.PMC10176977.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Measures of intracranial compartments in acute intracerebral haemorrhage: data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial (RIGHT-2). 急性脑出血颅内室室的测量:来自高血压卒中快速干预试验的数据(右2)。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2021-001375
Kailash Krishnan, Zhe Kang Law, Lisa J Woodhouse, Rob A Dineen, Nikola Sprigg, Joanna M Wardlaw, Philip M Bath

Background and purpose: Intracerebral haemorrhage volume (ICHV) is prognostically important but does not account for intracranial volume (ICV) and cerebral parenchymal volume (CPV). We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional outcomes. We also assessed if cistern effacement, midline shift, old infarcts, leukoaraiosis and brain atrophy were associated with outcomes.

Methods: Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were analysed. Measures included ICHV (using ABC/2) and ICV (XYZ/2) (by independent observers); ICHV, ICV and CPV (semiautomated segmentation, SAS); atrophy (intercaudate distance, ICD, Sylvian fissure ratio, SFR); midline shift; leukoaraiosis and cistern effacement (visual assessment). The effects of these measures on death at day 4 and poor functional outcome at day 90 (modified Rankin scale, mRS of >3) was assessed.

Results: ICV was significantly different between XYZ and SAS: mean (SD) of 1357 (219) vs 1420 (196), mean difference (MD) 62 mL (p<0.001). There was no significant difference in ICHV between ABC/2 and SAS. There was very good agreement for ICV measured by SAS, CPV, ICD, SFR, leukoaraiosis and cistern score (all interclass correlations, n=10: interobserver 0.72-0.99, intraobserver 0.73-1.00). ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90, death at day 4 and acute neurological deterioration (all p<0.05), similar to ICHV. Midline shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts, leukoaraiosis and brain atrophy were not.

Conclusions: Intracranial compartment measures and visual estimates are reproducible. ICHV adjusted for ICH and CPV could be useful to prognosticate in acute stroke. The presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

背景和目的:颅内出血量(ICHV)对预后有重要意义,但不能解释颅内体积(ICV)和脑实质体积(CPV)。我们使用计算机断层扫描评估急性脑出血患者颅内室室的测量,以及ICHV/ICV和ICHV/CPV是否预测功能结局。我们还评估了脑池淡化、中线移位、陈旧性梗死、白质变和脑萎缩是否与预后相关。方法:对高血压性卒中2期快速干预试验133例参与者的资料进行分析。测量包括ICHV(使用ABC/2)和ICV (XYZ/2)(由独立观察员);ICHV、ICV和CPV(半自动分割,SAS);萎缩(尾间距离,ICD, Sylvian裂隙比,SFR);中线移位;白质变和脑池淡化(目测)。评估这些措施对第4天死亡和第90天功能不良结局的影响(修正Rankin量表,mRS >3)。结果:XYZ和SAS之间的ICV有显著差异:平均(SD)为1357 (219)vs 1420(196),平均差(MD)为62 mL(结论:颅内间隔测量和视觉估计是可重复的。脑出血和脑脊液电位调整后的脑脊液电位可用于预测急性脑卒中患者的预后。中线移位和蓄水池消失的存在可以预测结果,但其机制需要在更大规模的研究中得到验证。
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引用次数: 0
Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI. 在7特斯拉MRI上,脑小血管病变的深部白质高强度与MRI可见血管周围间隙在空间上相关。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001611
Yajing Huo, Yilin Wang, Cen Guo, Qianyun Liu, Lili Shan, Mingyuan Liu, Haibo Wu, Guanwu Li, Huihui Lv, Lingdan Lu, Yintin Zhou, Jianfeng Feng, Yan Han

Background: The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI.

Methods: Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS.

Results: Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS.

Conclusion: dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

背景:血管周围间隙(PVS)与白质高强度(WMH)之间的关系尚不清楚。WMH周围的正常白质(NAWM)也被发现与局灶性WMH的发展有关。本研究旨在利用7特斯拉(7T) MRI研究PVS、深度WMH (dWMH)和WMH周围NAWM之间的拓扑联系。方法:从我科和临床选取32例非合流性腰痛患者和16例非合流性腰痛患者。我们使用5分制比较了有和没有wmh患者的PVS负担。然后,与对侧半球参考部位(无WMH)比较每个dWMH周围1 cm半径内的扩张和PVS数量。在本研究中,我们将NAWM定义为每个dWMH周围1厘米半径内的区域。此外,我们还评估了dWMH与PVS之间的空间关系。结果:>5个dWMH患者(中位数为3)比无dWMH患者(中位数为2,p = 0.014)半膈中心PVS评分更高。我们发现,与参考部位相比,dWMH周围的NAWM扩张更大,PVS数量更多(p结论:dWMH、WMH周围的NAWM和mri可见的PVS在早期脑血管病中具有空间相关性。未来对WMH和NAWM的研究不应忽视mri可见pv。
{"title":"Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI.","authors":"Yajing Huo,&nbsp;Yilin Wang,&nbsp;Cen Guo,&nbsp;Qianyun Liu,&nbsp;Lili Shan,&nbsp;Mingyuan Liu,&nbsp;Haibo Wu,&nbsp;Guanwu Li,&nbsp;Huihui Lv,&nbsp;Lingdan Lu,&nbsp;Yintin Zhou,&nbsp;Jianfeng Feng,&nbsp;Yan Han","doi":"10.1136/svn-2022-001611","DOIUrl":"https://doi.org/10.1136/svn-2022-001611","url":null,"abstract":"<p><strong>Background: </strong>The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI.</p><p><strong>Methods: </strong>Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS.</p><p><strong>Results: </strong>Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS.</p><p><strong>Conclusion: </strong>dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/49/svn-2022-001611.PMC10176991.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
NOTCH2NLC expanded GGC repeats in patients with cerebral small vessel disease. NOTCH2NLC在脑血管疾病患者中扩增GGC重复序列。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001631
Yun-Chao Wang, Yu Fan, Wen-Kai Yu, Si Shen, Jia-Di Li, Yuan Gao, Yan Ji, Yu-Sheng Li, Lu-Lu Yu, Zi-Chen Zhao, Shan-Shan Li, Yao Ding, Chang-He Shi, Yu-Ming Xu

Objective: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease.

Methods: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD.

Results: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%.

Conclusion: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.

目的:人类特异性NOTCH2NLC基因的GGC重复扩增已被报道为神经元核内包涵病(NIID)的原因。鉴于NIID与脑血管病(CSVD)认知功能障碍的临床重叠,两种疾病在脑MRI t2 -液体衰减反转恢复序列上均表现为白质高信号,白质高信号是CSVD的主要神经影像学标志物。因此,我们假设GGC重复扩增也可能导致CSVD。为了进一步研究NOTCH2NLC GGC重复扩增与CSVD之间的关系,我们对814例CSVD患者进行了遗传分析。方法:我们对814例散发性CSVD患者的NOTCH2NLC进行了全面的GGC重复扩展筛查。他们的法泽卡得分大于等于3分。重复引物PCR和荧光扩增子长度分析用于鉴定GGC重复扩增,全外显子组测序用于检测先前报道的与CSVD相关基因的任何致病性突变。结果:我们发现9例(1.11%)患者具有致病性GGC重复扩增,范围从41到98个重复。NOTCH2NLC扩增GGC重复序列的次要等位基因频率为0.55%。结论:我们的研究结果表明,NOTCH2NLC中中长度和较长长度的GGC重复扩增与散发性CSVD有关。这为研究心血管疾病的发病机制提供了新的思路。
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引用次数: 4
Correction: Cilostazol and isosorbide mononitrate for the prevention of progression of : baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850). 校正:西洛他唑和单硝酸异山梨酯预防:腔隙干预试验-2 (LACI-2) (ISRCTN14911850)的基线数据和统计分析计划。
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2022-001816corr1
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引用次数: 1
Circulating endothelial microvesicles and their carried miR-125a-5p: potential biomarkers for ischaemic stroke. 循环内皮微泡及其携带的miR-125a-5p:缺血性卒中的潜在生物标志物
IF 5.9 1区 医学 Q1 Medicine Pub Date : 2023-04-01 DOI: 10.1136/svn-2021-001476
Xiaotang Ma, Xiaorong Liao, Jiehong Liu, Yan Wang, Xiang Wang, Yanfang Chen, Xiaojian Yin, Qunwen Pan
Background Endothelial microvesicles (EMVs) are closely associated with the status of endothelial cells (ECs). Our earlier study has shown that EMVs could exert protective roles in ECs by transferring their carried miR-125a-5p. However, whether circulating EMVs and their carried miR-125a-5p can be used as biomarkers in ischaemic stroke (IS) are remain unknown. Methods We recruited 72 subjects with IS, 60 subjects with high stroke risk and 56 age-matched controls. The circulating EMVs and their carried miR-125a-5p (EMV-miR-125a-5p) levels were detected. We used microRNA (miR) array to study expression changes of miRs in plasma EMVs samples of three IS patients and three matched healthy controls. Transient middle cerebral artery occlusion (tMCAO) was used to establish IS mouse model. Results EMVs level was obviously elevated in IS patients, with the highest level in acute stage, and was positively related to carotid plaque, carotid intima–media thickness (IMT), National Institutes of Health Stroke Scale (NIHSS), infarct volume. On the contrary, we observed that EMV-miR-125a-5p level was obviously reduced in IS, with the lowest level in acute stage, and was negatively correlated with carotid plaque, IMT, NIHSS scores, infarct volume. EMVs and EMV-miR-125a-5p levels were closely related with large artery atherosclerosis subgroup. Importantly, EMVs and EMV-miR-125a-5p levels could serve as independent risk factors, and receiver operating characteristic curve achieved an area under curve (AUC) of 0.720 and 0.832 for IS, respectively, and elevated to 0.881 after their combination. In IS mouse model, control EMVs or n-EMVs administration could decrease the infarct volume and neurological deficit score, while increase the cerebral blood flow of IS mice compared with vehicle group, while IS EMVs or oxygen and glucose deprivation (OGD)-EMVs administration aggravated the tMCAO induced ischaemic injury. In addition, we observed that OGD EMVmiR-125a-5p could partially ameliorate the OGD EMVs induced brain injury after IS. Conclusions These findings demonstrate that circulating EMVs and EMV-miR-125a-5p are closely related with the occurrence, progress, subtypes and severity of IS, and they can serve as innovative biomarkers and therapeutic targets for IS, especially when they are combined.
背景:内皮微泡(emv)与内皮细胞(ECs)的状态密切相关。我们早期的研究表明,emv可以通过转移其携带的miR-125a-5p在ECs中发挥保护作用。然而,循环emv及其携带的miR-125a-5p是否可以作为缺血性卒中(IS)的生物标志物仍然未知。方法:我们招募了72名IS患者,60名卒中高危患者和56名年龄匹配的对照组。检测循环emv及其携带的miR-125a-5p (EMV-miR-125a-5p)水平。我们使用microRNA (miR)阵列研究了3例IS患者和3例匹配的健康对照的血浆emv样本中miR的表达变化。采用短暂性大脑中动脉闭塞(tMCAO)建立IS小鼠模型。结果:IS患者emv水平明显升高,以急性期最高,且与颈动脉斑块、颈动脉内膜-中膜厚度(IMT)、美国国立卫生研究院卒中量表(NIHSS)、梗死体积呈正相关。相反,我们观察到EMV-miR-125a-5p水平在IS中明显降低,急性期最低,且与颈动脉斑块、IMT、NIHSS评分、梗死体积呈负相关。emv和EMV-miR-125a-5p水平与大动脉粥样硬化亚组密切相关。重要的是,emv和EMV-miR-125a-5p水平可以作为独立的危险因素,IS的受试者工作特征曲线的曲线下面积(AUC)分别为0.720和0.832,两者联合后升高至0.881。在IS小鼠模型中,与对照组相比,对照emv或n- emv给药可降低IS小鼠梗死面积和神经功能缺损评分,增加脑血流量,而IS emv或氧葡萄糖剥夺(OGD)- emv给药可加重tMCAO诱导的缺血损伤。此外,我们观察到OGD EMVmiR-125a-5p可以部分改善IS后OGD emv诱导的脑损伤。结论:这些研究结果表明,循环emv和EMV-miR-125a-5p与IS的发生、进展、亚型和严重程度密切相关,它们可以作为IS的创新生物标志物和治疗靶点,特别是当它们联合使用时。
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引用次数: 2
期刊
Stroke and Vascular Neurology
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