Xin Tong, Quanhe Yang, Ganesh Asaithambi, Robert K Merritt
{"title":"Venous thromboembolism among Medicare acute ischaemic stroke patients with and without COVID-19.","authors":"Xin Tong, Quanhe Yang, Ganesh Asaithambi, Robert K Merritt","doi":"10.1136/svn-2022-001814","DOIUrl":"https://doi.org/10.1136/svn-2022-001814","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is associated with an increased risk of venous thromboembolism (VTE). This study examined the prevalence of VTE among acute ischaemic stroke (AIS) patients with and without a history of COVID-19.</p><p><strong>Methods: </strong>We identified AIS hospitalisations of Medicare fee-for-service (FFS) beneficiaries aged ≥65 years from 1 April 2020 to 31 March 2022. We compared the prevalence and adjusted prevalence ratio of VTE among AIS patients with and without a history of COVID-19.</p><p><strong>Results: </strong>Among 283 034 Medicare FFS beneficiaries with AIS hospitalisations, the prevalence of VTE was 4.51%, 2.96% and 2.61% among those with a history of hospitalised COVID-19, non-hospitalised COVID-19 and without COVID-19, respectively. As compared with patients without a history of COVID-19, the prevalence of VTE among patients with a history of hospitalised or non-hospitalised COVID-19 were 1.62 (95% CI 1.54 to 1.70) and 1.13 (95% CI 1.03 to 1.23) times greater, respectively.</p><p><strong>Conclusions: </strong>There appeared to be a notably higher prevalence of VTE among Medicare beneficiaries with AIS accompanied by a current or prior COVID-19. Early recognition of coagulation abnormalities and appropriate interventions may help improve patients' clinical outcomes.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"259-262"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/37/svn-2022-001814.PMC10359775.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10092775","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}
James J M Loan, Steven Tominey, Kirun Baweja, Julie Woodfield, Thomas J G Chambers, Mark Haley, Simran S Kundu, H Y Josephine Tang, Anthony N Wiggins, Michael T C Poon, Paul M Brennan
{"title":"Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland.","authors":"James J M Loan, Steven Tominey, Kirun Baweja, Julie Woodfield, Thomas J G Chambers, Mark Haley, Simran S Kundu, H Y Josephine Tang, Anthony N Wiggins, Michael T C Poon, Paul M Brennan","doi":"10.1136/svn-2022-001583","DOIUrl":"https://doi.org/10.1136/svn-2022-001583","url":null,"abstract":"<p><strong>Background: </strong>Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH.</p><p><strong>Methods: </strong>We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression.</p><p><strong>Results: </strong>175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I-III, modified Fisher 2-4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia.</p><p><strong>Conclusions: </strong>In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"207-216"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034922","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}
{"title":"Editorial: minor stroke is not minor.","authors":"Xinyi Leng, David Wang","doi":"10.1136/svn-2022-002049","DOIUrl":"https://doi.org/10.1136/svn-2022-002049","url":null,"abstract":"","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"175-177"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/53/svn-2022-002049.PMC10359791.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032894","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}
Sabine L Collette, Michael P Rodgers, Marianne A A van Walderveen, Kars C J Compagne, Paul J Nederkoorn, Jeannette Hofmeijer, Jasper M Martens, Gert J de Borst, Gert Jan R Luijckx, Charles B L M Majoie, Aad van der Lugt, Reinoud P H Bokkers, Maarten Uyttenboogaart
{"title":"Management of extracranial carotid artery stenosis during endovascular treatment for acute ischaemic stroke: results from the MR CLEAN Registry.","authors":"Sabine L Collette, Michael P Rodgers, Marianne A A van Walderveen, Kars C J Compagne, Paul J Nederkoorn, Jeannette Hofmeijer, Jasper M Martens, Gert J de Borst, Gert Jan R Luijckx, Charles B L M Majoie, Aad van der Lugt, Reinoud P H Bokkers, Maarten Uyttenboogaart","doi":"10.1136/svn-2022-001891","DOIUrl":"https://doi.org/10.1136/svn-2022-001891","url":null,"abstract":"<p><strong>Background: </strong>The optimal management of ipsilateral extracranial internal carotid artery (ICA) stenosis during endovascular treatment (EVT) is unclear. We compared the outcomes of two different strategies: EVT with vs without carotid artery stenting (CAS).</p><p><strong>Methods: </strong>In this observational study, we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of ≥50% or occlusion of presumed atherosclerotic origin, from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry (2014-2017). The primary endpoint was a good functional outcome at 90 days, defined as a modified Rankin Scale score ≤2. Secondary endpoints were successful intracranial reperfusion, new clot in a different vascular territory, symptomatic intracranial haemorrhage, recurrent ischaemic stroke and any serious adverse event.</p><p><strong>Results: </strong>Of the 433 included patients, 169 (39%) underwent EVT with CAS. In 123/168 (73%) patients, CAS was performed before intracranial thrombectomy. In 42/224 (19%) patients who underwent EVT without CAS, a deferred carotid endarterectomy or CAS was performed. EVT with and without CAS were associated with similar proportions of good functional outcome (47% vs 42%, respectively; adjusted OR (aOR), 0.90; 95% CI, 0.50 to 1.62). There were no major differences between the groups in any of the secondary endpoints, except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group (aOR, 2.96; 95% CI, 1.07 to 8.21).</p><p><strong>Conclusions: </strong>Functional outcomes were comparable after EVT with and without CAS. CAS during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"229-237"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/6c/svn-2022-001891.PMC10359798.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10092785","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}
Dar Dowlatshahi, Cheemun Lum, Bijoy K Menon, Aditya Bharatha, Prasham Dave, Paulo Puac-Polanco, Dylan Blacquiere, Grant Stotts, Michel Shamy, Franco Momoli, Rebecca Thornhill, Ronda Lun, Carlos Torres
{"title":"Aetiology of extracranial carotid free-floating thrombus in a prospective multicentre cohort.","authors":"Dar Dowlatshahi, Cheemun Lum, Bijoy K Menon, Aditya Bharatha, Prasham Dave, Paulo Puac-Polanco, Dylan Blacquiere, Grant Stotts, Michel Shamy, Franco Momoli, Rebecca Thornhill, Ronda Lun, Carlos Torres","doi":"10.1136/svn-2022-001639","DOIUrl":"https://doi.org/10.1136/svn-2022-001639","url":null,"abstract":"<p><strong>Background: </strong>Carotid free-floating thrombi (FFT) in patients with acute transient ischaemic attack (TIA)/stroke have a high risk of early recurrent stroke. Management depends on aetiology, which can include local plaque rupture, dissection, coagulopathy, malignancy and cardioembolism. Our objectives were to classify the underlying aetiology of FFT and to estimate the proportion of patients with underlying stenosis requiring revascularisation.</p><p><strong>Methods: </strong>We prospectively enrolled consecutive patients presenting to three comprehensive stroke centres with acute TIA/stroke and ipsilateral internal carotid artery FFT. The aetiology of FFT was classified as: carotid atherosclerotic disease, carotid dissection, cardioembolism, both carotid atherosclerosis and cardioembolism, or embolic stroke of uncertain source (ESUS). Patients with carotid atherosclerosis were further subclassified as having ≥50% or <50% stenosis.</p><p><strong>Results: </strong>We enrolled 83 patients with confirmed FFT. Aetiological assessments revealed 66/83 (79.5%) had carotid atherosclerotic plaque, 4/83 (4.8%) had a carotid dissection, 10/83 (12%) had both atrial fibrillation and carotid atherosclerotic plaque and 3/83 (3.6%) were classified as ESUS. Of the 76 patients with atherosclerotic plaque (including those with atrial fibrillation), 40 (52.6%) had ≥50% ipsilateral stenosis.</p><p><strong>Conclusions: </strong>The majority of symptomatic carotid artery FFT are likely caused by local plaque rupture, more than half of which are associated with moderate to severe carotid stenosis requiring revascularisation. However, a significant number of FFTs are caused by non-atherosclerotic mechanisms warranting additional investigations.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"194-196"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/48/svn-2022-001639.PMC10359789.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841861","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}
{"title":"COP27 climate change conference: urgent action needed for Africa and the world.","authors":"Chris Zielinski","doi":"10.1136/svn-2022-002080","DOIUrl":"https://doi.org/10.1136/svn-2022-002080","url":null,"abstract":"The 2022 report of the Intergovernmental Panel on Climate Change paints a dark picture of the future of life on earth, characterised by ecosystem collapse, species extinction and climate hazards such as heatwaves and floods. These are all linked to physical and mental health problems, with direct and indirect consequences of increased morbidity and mortality. To avoid these catastrophic health effects across all regions of the globe, there is broad agreement—as 231 health journals argued together in 2021—that the rise in global temperature must be limited to <1.5°C compared with preindustrial levels. While the Paris Agreement of 2015 outlines a global action framework that incorporates providing climate finance to lowincome and middleincome countries, this support has yet to materialise. COP27 is the fifth Conference of the Parties (COP) to be organised in Africa since its inception in 1995. Ahead of this meeting, we—as health journal editors from across the continent—call for urgent action to ensure it is the COP that finally delivers climate justice for Africa and vulnerable countries. This is essential for the health of those countries, and for the health of the whole world.","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"178-180"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9849393","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}
Yeying Sun, Tao Wang, Yan Lv, Jiahua Li, Xiaoli Jiang, Jing Jiang, Daolai Zhang, Weihua Bian, Chunxiang Zhang
{"title":"MALAT1 promotes platelet activity and thrombus formation through PI3k/Akt/GSK-3β signalling pathway.","authors":"Yeying Sun, Tao Wang, Yan Lv, Jiahua Li, Xiaoli Jiang, Jing Jiang, Daolai Zhang, Weihua Bian, Chunxiang Zhang","doi":"10.1136/svn-2022-001498","DOIUrl":"https://doi.org/10.1136/svn-2022-001498","url":null,"abstract":"<p><strong>Background: </strong>Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis, which rely on platelet activity. In platelets, a wide variety of microRNAs (long non-coding RNA, lncRNAs) is found. Due to the absence of nuclear DNA in platelets, lncRNAs may serve as critical post-transcriptional regulators of platelet activities. However, research into the roles of lncRNAs in platelets is limited.</p><p><strong>Objective: </strong>The purpose of this study is to learn more about the molecular mechanism by which MALAT1 affects platelet activity and thrombus formation.</p><p><strong>Methods/results: </strong>The CD34<sup>+</sup> megakaryocytes used in this research as an in vitro model for human megakaryocytes and platelets. Cell adhesion and spreading are enhanced in the absence and presence of agonists in CD34<sup>+</sup> megakaryocytes subjected to MALAT1 knockdown (KD). The adhesion and activity of platelet-like particles produced by MALAT1 KD cells are significantly enhanced at rest and after thrombin activation. Thrombus development on a collagen matrix is also greatly enhanced in the microfluidic whole-blood perfusion model: platelets lacking MALAT1 exhibit elevated accumulation, distributing area and activity. In addition, MALAT1-deficient mice bleed less and form a stable occlusive thrombus more quickly than wild-type mice. PTEN and PDK1 regulated the activity of MALAT1 in platelets to carry out its PI3k/Akt/GSK-3β signalling pathway-related function.</p><p><strong>Conclusion: </strong>The suppression of MALAT1 expression significantly increases platelet adhesion, spreading, platelet activity, and thrombus formation. lncRNAs may constitute a unique class of platelet function modulators.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"181-192"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/c2/svn-2022-001498.PMC10359792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10391341","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}
Hongyuan Xu, Ran Huo, Hao Li, Yuming Jiao, Jiancong Weng, Jie Wang, Zihan Yan, Junze Zhang, Shaozhi Zhao, Qiheng He, Yingfan Sun, Shuo Wang, Yong Cao
{"title":"KRAS mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-β/BMP-SMAD4 pathway.","authors":"Hongyuan Xu, Ran Huo, Hao Li, Yuming Jiao, Jiancong Weng, Jie Wang, Zihan Yan, Junze Zhang, Shaozhi Zhao, Qiheng He, Yingfan Sun, Shuo Wang, Yong Cao","doi":"10.1136/svn-2022-001700","DOIUrl":"https://doi.org/10.1136/svn-2022-001700","url":null,"abstract":"<p><strong>Objective: </strong>Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (bAVMs), and subsequent in vivo experiments have confirmed that KRAS mutation in endothelial cells (ECs) causes AVMs in mouse and zebrafish models. Our previous study demonstrated that the KRAS<sup>G12D</sup> mutant independently induced the endothelial-mesenchymal transition (EndMT), which was reversed by treatment with the lipid-lowering drug lovastatin. However, the underlying mechanisms of action were unclear.</p><p><strong>Methods: </strong>We used human umbilical vein ECs (HUVECs) overexpressing the KRAS<sup>G12D</sup> mutant for Western blotting, quantitative real-time PCR, and immunofluorescence and wound healing assays to evaluate the EndMT and determine the activation of downstream pathways. Knockdown of SMAD4 by RNA interference was performed to explore the role of SMAD4 in regulating the EndMT. BAVM ECs expressing the KRAS<sup>G12D</sup> mutant were obtained to verify the SMAD4 function. Finally, we performed a coimmunoprecipitation assay to probe the mechanism by which lovastatin affects SMAD4.</p><p><strong>Results: </strong>HUVECs infected with KRAS<sup>G12D</sup> adenovirus underwent the EndMT. Transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signalling pathways were activated in the KRAS<sup>G12D</sup>-mutant HUVECs and ECs in bAVM tissue. Knocking down SMAD4 expression in both KRAS<sup>G12D</sup>-mutant HUVECs and ECs in bAVM tissues inhibited the EndMT. Lovastatin attenuated the EndMT by downregulating p-SMAD2/3, p-SMAD1/5 and acetylated SMAD4 expression in KRAS<sup>G12D</sup>-mutant HUVECs.</p><p><strong>Conclusions: </strong>Our findings suggest that the KRAS<sup>G12D</sup> mutant induces the EndMT by activating the ERK-TGF-β/BMP-SMAD4 signalling pathway and that lovastatin inhibits the EndMT by suppressing TGF-β/BMP pathway activation and SMAD4 acetylation.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"197-206"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/e3/svn-2022-001700.PMC10359780.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10032878","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}
Jie Zhang, Haiying Li, Zhongmou Xu, Jinxin Lu, Chang Cao, Haitao Shen, Xiang Li, Wanchun You, Gang Chen
{"title":"Oestrogen ameliorates blood-brain barrier damage after experimental subarachnoid haemorrhage via the SHH pathway in male rats.","authors":"Jie Zhang, Haiying Li, Zhongmou Xu, Jinxin Lu, Chang Cao, Haitao Shen, Xiang Li, Wanchun You, Gang Chen","doi":"10.1136/svn-2022-001907","DOIUrl":"https://doi.org/10.1136/svn-2022-001907","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>In conclusion, we demonstrate here that oestrogen pretreatment ameliorates brain injury after SAH, at least in part through SHH pathway-mediated BBB protection.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 3","pages":"217-228"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/44/svn-2022-001907.PMC10359806.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034949","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}
{"title":"Endovascular therapy in acute anterior circulation large vessel occlusive patients with a large infarct core (ANGEL-ASPECT): protocol of a multicentre randomised trial.","authors":"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","doi":"10.1136/svn-2022-001865","DOIUrl":"https://doi.org/10.1136/svn-2022-001865","url":null,"abstract":"<p><strong>Background: </strong>The benefit of stroke thrombectomy for large infarct core still lacks robust randomised controlled studies.</p><p><strong>Aim: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Study outcomes: </strong>The primary efficacy outcome is 90 (±7) days modified Rankin Scale. Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"169-174"},"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/30/4c/svn-2022-001865.PMC10176983.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557094","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}