Translational Stroke Research最新文献

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Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1): A Potential Therapeutic Target in Ischemic Stroke. 类似凝集素的氧化低密度脂蛋白受体-1 (LOX-1):缺血性中风的潜在治疗靶点。
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-22 DOI: 10.1007/s12975-024-01307-z
Yue Hu, Yuhao Li, Yumin Luo, Ningqun Wang, Yangmin Zheng
{"title":"Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1): A Potential Therapeutic Target in Ischemic Stroke.","authors":"Yue Hu, Yuhao Li, Yumin Luo, Ningqun Wang, Yangmin Zheng","doi":"10.1007/s12975-024-01307-z","DOIUrl":"https://doi.org/10.1007/s12975-024-01307-z","url":null,"abstract":"<p><p>Stroke, the leading cause of disability and the second leading cause of death worldwide, is characterized by high morbidity and disability. The lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that promotes endothelial dysfunction by recognizing and internalizing oxidized low-density lipoproteins (ox-LDL) to induce the formation, development, and instability of atherosclerotic plaques, ultimately leading to vascular thrombosis. Previous clinical and epidemiological studies have indicated that LOX-1 plays a vital role in cerebral ischemic injury following ischemic stroke. Multiple clinical studies have shown that the genetic polymorphisms in LOX-1 are associated with susceptibility to ischemic stroke. Soluble LOX-1 (sLOX-1), a biomarker of ischemic stroke, is associated with the prognosis of ischemic stroke. This article discusses the clinical and experimental findings on LOX-1 in ischemic stroke and the development of new therapeutic strategies targeting LOX-1.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cilostazol Alleviates Delayed Cerebral Ischemia After Subarachnoid Hemorrhage by Attenuating Microcirculatory Dysfunction. 西洛他唑通过减轻微循环功能障碍缓解蛛网膜下腔出血后的延迟性脑缺血
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-20 DOI: 10.1007/s12975-024-01308-y
Masato Naraoka, Norihito Shimamura, Hiroki Ohkuma
{"title":"Cilostazol Alleviates Delayed Cerebral Ischemia After Subarachnoid Hemorrhage by Attenuating Microcirculatory Dysfunction.","authors":"Masato Naraoka, Norihito Shimamura, Hiroki Ohkuma","doi":"10.1007/s12975-024-01308-y","DOIUrl":"https://doi.org/10.1007/s12975-024-01308-y","url":null,"abstract":"<p><p>Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor that exerts antiplatelet effects, has therapeutic potential for delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, its mechanism of action remains unclear. We hypothesized that cilostazol alleviates DCI by improving cerebral microcirculatory dysfunction, which is a component of early brain injury. To test this hypothesis, we analyzed the intracerebral circulation time (iCCT) in 256 patients with aSAH from two randomized controlled trials (74 received cilostazol, 54 received pitavastatin, and 128 were controls). A minority of patients (n = 72, 28%) developed severe angiographic vasospasm (aVS) and DCI (n = 42, 16%) and had poor outcomes (n = 35, 14%). We measured iCCT as the time to peak in the ultraearly phase (baseline) and the subacute phase or at DCI onset (follow-up). The cilostazol group had shorter follow-up iCCT and larger iCCT differences than the other groups, indicating improved microcirculatory function, particularly in patients with DCI and poor outcomes. Multivariate analysis revealed that cilostazol treatment is a significant predictor of favorable outcomes, whereas DCI occurrence, a decrease in iCCT differences, and high clinical severity (Hunt & Hess grades 3-4) were associated with poor outcomes. Diminished microcirculatory dysfunction may alleviate DCI and improve outcomes among patients with aSAH following cilostazol treatment. Further research is warranted to confirm these findings and explore the dose-dependent effects of cilostazol on the microcirculatory function.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Rat Model of Embolic Cerebral Ischemia Using a Radiopaque Blood Clot and a Microcatheter Under Fluoroscopy. 在透视下使用不透射线血凝块和微导管建立栓塞性脑缺血的新型大鼠模型
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-19 DOI: 10.1007/s12975-024-01312-2
Teppei Komatsu, Hiroki Ohta, Misato Takeda, Yasuhiro Matsumura, Masayuki Yokoyama, Zuojun Wang, Hirotaka James Okano, Yasuyuki Iguchi
{"title":"Novel Rat Model of Embolic Cerebral Ischemia Using a Radiopaque Blood Clot and a Microcatheter Under Fluoroscopy.","authors":"Teppei Komatsu, Hiroki Ohta, Misato Takeda, Yasuhiro Matsumura, Masayuki Yokoyama, Zuojun Wang, Hirotaka James Okano, Yasuyuki Iguchi","doi":"10.1007/s12975-024-01312-2","DOIUrl":"10.1007/s12975-024-01312-2","url":null,"abstract":"<p><p>Conventional rat models of thromboembolic stroke do not allow control of infarct size or spontaneous recanalization. We aimed to develop a novel rat thromboembolic stroke model that ensures highly reproducible infarct sizes and locations within the MCA territory and does not require arterial ligation. Twenty male Sprague-Dawley rats and two sham-operated rats were included. A microcatheter was navigated from the caudal ventral artery to the internal carotid artery using digital subtraction angiography. A blood clot (diameter, 0.86 mm; length, 3 mm) containing zirconium dioxide was advanced in the catheter. Fluoroscopy was performed at 1, 3, 6, and 24 h after stroke model creation, and TTC staining was conducted at 24 h. Neurological deficit scores were measured. In all embolized rats, the ACA and MCA bifurcation were selective. Median operating time was 6 min. The position of the radiopaque blood clot remained unchanged for 24 h after model creation in 19/20 rats. Median infarct volume was 242 mm<sup>3</sup> (IQR, 239-262 mm<sup>3</sup>). We present a novel rat model of highly reproducible focal infarct in only the MCA territory. Fluoroscopy effectively identified any blood clot migration. This model could contribute to the development of new thrombolytic agents.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke. 光血栓性中风后儿茶酚胺诱导的心脏炎症组活化
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-18 DOI: 10.1007/s12975-024-01311-3
Xavier O Scott, Nadine A Kerr, Juliana Sanchez-Molano, Juan Pablo de Rivero Vaccari, Roey Hadad, Alicia De La Cruz, H Peter Larsson, W Dalton Dietrich, Robert W Keane
{"title":"Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke.","authors":"Xavier O Scott, Nadine A Kerr, Juliana Sanchez-Molano, Juan Pablo de Rivero Vaccari, Roey Hadad, Alicia De La Cruz, H Peter Larsson, W Dalton Dietrich, Robert W Keane","doi":"10.1007/s12975-024-01311-3","DOIUrl":"https://doi.org/10.1007/s12975-024-01311-3","url":null,"abstract":"<p><p>Cerebrovascular stroke patients exhibit an increased incidence of cardiac arrhythmias. The pathomechanisms underlying post-traumatic cardiac dysfunction include a surge of catecholamines and an increased systemic inflammatory response, but whether inflammasome activation contributes to cardiac dysfunction remains unexplored. Here, we used a mouse model of photothrombotic stroke (PTS) to investigate the role of inflammasome activation in post-stroke cardiac dysfunction by catecholamines and to evaluate the effectiveness of the inflammasome inhibitor IC100 on inflammasome activation. To evaluate functional electrophysiological changes in the heart by catecholamine treatment, we recorded action potential duration in excised zebrafish hearts with and without IC100 treatment. We show that PTS induced AIM2 inflammasome activation in atria and ventricles that was significantly reduced by administration of IC100. Injection of epinephrine into naïve mice induced a significant increase in AIM2, IL-1b and caspase-8 in atria. Treatment of excised zebrafish hearts with epinephrine shortened the action potential duration and this shortening that was reduced by IC100. These findings indicate that stroke initiates a catecholamine surge that induces inflammasome activation and pyroptosis in the heart that is blocked by IC100, thus providing a framework for the development of therapeutics for stroke-related cardiovascular injury.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease. 颅内动脉粥样硬化病流动依赖性内皮化三维模型的开发与验证
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-14 DOI: 10.1007/s12975-024-01310-4
Grace Prochilo, Chuanlong Li, Eleni Miliotou, Russell Nakasone, Alissa Pfeffer, Charles Beaman, Naoki Kaneko, David S Liebeskind, Jason D Hinman
{"title":"Development and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease.","authors":"Grace Prochilo, Chuanlong Li, Eleni Miliotou, Russell Nakasone, Alissa Pfeffer, Charles Beaman, Naoki Kaneko, David S Liebeskind, Jason D Hinman","doi":"10.1007/s12975-024-01310-4","DOIUrl":"https://doi.org/10.1007/s12975-024-01310-4","url":null,"abstract":"<p><p>Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted TGF-βR2 Silencing in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke. 在伴有或不伴有中风的脑淀粉样变性血管病小鼠模型中,靶向抑制视网膜上皮细胞核的 TGF-βR2 可减轻呼吸功能障碍和认知能力下降。
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-14 DOI: 10.1007/s12975-024-01306-0
Ahmad El Hamamy, Zahid Iqbal, Ngoc Mai Le, Arya Ranjan, YuXing Zhang, Hung Wen Lin, Chunfeng Tan, Destiny Sumani, Anthony Patrizz, Louise D McCullough, Jun Li
{"title":"Targeted TGF-βR2 Silencing in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke.","authors":"Ahmad El Hamamy, Zahid Iqbal, Ngoc Mai Le, Arya Ranjan, YuXing Zhang, Hung Wen Lin, Chunfeng Tan, Destiny Sumani, Anthony Patrizz, Louise D McCullough, Jun Li","doi":"10.1007/s12975-024-01306-0","DOIUrl":"10.1007/s12975-024-01306-0","url":null,"abstract":"<p><p>Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO<sub>2</sub> sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-β) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke. Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-βR2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-βR2 and GFAP expressions in the RTN. CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-βR2 silencing in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-βR2 silencing similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-βR2 and GFAP expressions in the RTN following silencing. Our findings demonstrate that increased TGF-β signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-βR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNF213 p.Arg4810Lys Variant Is Associated with Higher Stenosis Progression in Asymptomatic Intracranial Artery Stenosis. RNF213 p.Arg4810Lys变异与无症状颅内动脉狭窄进展较快有关。
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-12 DOI: 10.1007/s12975-024-01309-x
Shogo Dofuku, Satoru Miyawaki, Hideaki Imai, Masahiro Shimizu, Hiroki Hongo, Yuki Shinya, Kenta Ohara, Yu Teranishi, Hideaki Ono, Hirofumi Nakatomi, Akira Teraoka, Nobuhito Saito
{"title":"RNF213 p.Arg4810Lys Variant Is Associated with Higher Stenosis Progression in Asymptomatic Intracranial Artery Stenosis.","authors":"Shogo Dofuku, Satoru Miyawaki, Hideaki Imai, Masahiro Shimizu, Hiroki Hongo, Yuki Shinya, Kenta Ohara, Yu Teranishi, Hideaki Ono, Hirofumi Nakatomi, Akira Teraoka, Nobuhito Saito","doi":"10.1007/s12975-024-01309-x","DOIUrl":"https://doi.org/10.1007/s12975-024-01309-x","url":null,"abstract":"<p><p>Intracranial artery stenosis (ICAS) is a significant contributor to ischemic stroke, with the RNF213 p.Arg4810Lys variant identified as a related genetic factor. We explored the clinical outcomes of the RNF213 genotype in patients with asymptomatic ICAS. Between November 2011 and March 2019, 139 patients with asymptomatic ICAS were enrolled in this study. Genotyping for RNF213 p.Arg4810Lys was performed using Sanger sequencing. A comprehensive analysis was conducted to compare the RNF213 genotype with background characteristics and clinical outcomes such as ipsilateral ischemic cerebrovascular events and stenosis progression. RNF213 p.Arg4810Lys was found in 25% of cases, revealing distinct clinical features between carriers and non-carriers. The incidence of ipsilateral ischemic cerebrovascular events was 4.3% (6/139 cases), and stenosis progression was observed in 13% (18/139 cases) during a mean follow-up period of 58 months. Stenosis progression rates were notably higher in the RNF213 variant group (25.7%; 9/35 cases) than in the RNF213 wild-type group (8.7%; 9/104 cases). Cumulative stenosis progression rate was significantly higher in the RNF213 variant group than in the RNF213 wild-type group (log-rank test, P = 0.0004). Multivariate Cox regression analysis indicated a significant association between the RNF213 p.Arg4810Lys variant and an increased risk of stenosis progression (P = 0.03, odds ratio 3.2; 95% confidence interval, 1.1-9.0). The RNF213 p.Arg4810Lys variant exhibits clinical disparities in asymptomatic ICAS and is notably linked to a heightened risk of stenosis progression. These results suggest a distinct difference in the vascular stenosis mechanism associated with this variant, warranting further investigation into its clinical implications and potential mechanistic insights.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blockade of the Platelet-Driven CXCL7-CXCR1/2 Inflammatory Axis Prevents Murine Cerebral Aneurysm Formation and Rupture. 阻断血小板驱动的 CXCL7-CXCR1/2 炎症轴可预防小鼠脑动脉瘤的形成和破裂
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-05 DOI: 10.1007/s12975-024-01304-2
Kamil W Nowicki, Aditya Mittal, Joseph S Hudson, Michael P D'Angelo, Michael M McDowell, Catherine Cao, Rohit Mantena, Abhishek Jauhari, Robert M Friedlander
{"title":"Blockade of the Platelet-Driven CXCL7-CXCR1/2 Inflammatory Axis Prevents Murine Cerebral Aneurysm Formation and Rupture.","authors":"Kamil W Nowicki, Aditya Mittal, Joseph S Hudson, Michael P D'Angelo, Michael M McDowell, Catherine Cao, Rohit Mantena, Abhishek Jauhari, Robert M Friedlander","doi":"10.1007/s12975-024-01304-2","DOIUrl":"https://doi.org/10.1007/s12975-024-01304-2","url":null,"abstract":"<p><p>Platelet aggregation is intimately associated with vascular inflammation and is commonly seen on routine histology studies of cerebral aneurysms. Platelets, when activated, have been shown to augment neutrophil response and the pro-inflammatory cascade. Platelet-neutrophil complexes have been found to aggravate atherosclerosis through a positive feedback loop. We hypothesized that targeting platelet aggregation and downstream inflammation could be used to prevent aneurysm formation and progression. First, we induced cerebral aneurysm formation in a previously described intracranial aneurysm model via carotid artery ligation, hypertension, and stereotactic elastase injection in C57BL/6 mice and analyzed vessels for lesion and thrombus formation. Raybiotech cytokine arrays were used to analyze 96 cytokines in induced murine aneurysms and 120 cytokines in human tissue samples. Cerebral aneurysm formation and inflammatory pathway were then studied in animals treated with IgG2 antibody (control), anti-GpIb antibody (platelet depletion), 1:10 DMSO:PBS (control), clopidogrel, anti-CXCR1/2 small molecule inhibitor, or anti-CXCL7 antibody. Bleeding assays and flow cytometry were used to evaluate platelet function in treated groups. CD31 + platelet aggregates are a common feature in human and mouse cerebral aneurysm specimens. Platelet ablation in mice prevents cerebral aneurysm formation (20% vs 100% in control antibody-treated mice, n = 5 each, p = 0.0476). Mice treated with 1 mg/kg clopidogrel develop significantly less aneurysms than controls (18% vs 73%, n = 11 and 11, respectively, p = 0.03). Semi-quantitative analysis of 96 different cytokines using Raybiotech arrays shows increased protein expression of CXCL7 in murine cerebral aneurysms when compared to controls. Treatment with clopidogrel results in reciprocal decrease in detected CXCL7. Targeting CXCL7-CXCR1/2 axis with 10 mg/kg reparixin (CXCR1/2 antagonist) significantly decreases cerebral aneurysm formation (11% vs 73%, n = 9 and 11, p = 0.0098) while treatment with 10 mg/kg SB225002 tends to decrease aneurysm formation (36% vs 73%, n = 11 vs n = 7, p = 0.11). Lastly, specific antibody blockade against CXCL7 using anti-CXCL7 antibody at 100 ug/mL significantly decreases cerebral aneurysm formation (29% vs 75%, n = 7 vs n = 8, p = 0.046). Platelet inflammation has an important role in cerebral aneurysm formation. Small molecule inhibitors targeting platelet CXCL7-CXCR1/2 inflammatory axis could be used to prevent cerebral aneurysm formation or progression.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inverse Association between the Body Mass Index and the Incidence of Unruptured Intracranial Aneurysms-Insights from the Hamburg City Health Population Study. 身体质量指数与未破裂颅内动脉瘤发病率之间的反向关系--汉堡市健康人口研究的启示。
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-11-04 DOI: 10.1007/s12975-024-01305-1
Paul Steffen, Laurens Winkelmeier, Christian Heitkamp, Christian Thaler, Gabriel Broocks, Vincent Geest, Tobias D Faizy, Caspar Brekenfeld, Jens Fiehler, Thomas Lindner, Maria T Nawka
{"title":"Inverse Association between the Body Mass Index and the Incidence of Unruptured Intracranial Aneurysms-Insights from the Hamburg City Health Population Study.","authors":"Paul Steffen, Laurens Winkelmeier, Christian Heitkamp, Christian Thaler, Gabriel Broocks, Vincent Geest, Tobias D Faizy, Caspar Brekenfeld, Jens Fiehler, Thomas Lindner, Maria T Nawka","doi":"10.1007/s12975-024-01305-1","DOIUrl":"https://doi.org/10.1007/s12975-024-01305-1","url":null,"abstract":"<p><p>Overweight/obese patients experience a lower incidence of subarachnoid hemorrhage (SAH) compared to non-overweight patients, even though elevated body mass index (BMI) has been associated with various SAH risk factors. Given that intracranial aneurysms are a primary cause of SAH, a potential protective effect of a high BMI on intracranial aneurysms is likely but remains insufficiently investigated. This population-based MRI study aims to conduct detailed analyses on risk factors associated with the incidence of unruptured intracranial aneurysms (UIA). Retrospective analysis of subjects enrolled in the prospective Hamburg City Health study who underwent intracranial magnetic resonance imaging (MRI) was done. MRI scans were screened for UIA using time-of-flight angiography. Subject data including medical history, laboratory examinations, and risk factors for UIA were collected, and a multivariable logistic regression model was used to investigate the relationship between risk factors and UIA incidence. 2688 subjects (mean (IQR) age, 65 (58-71); 1176 female (43.8%) were included. An UIA was detected in 214 subjects with an incidence of 10.6% (6.0%) in females (males). Determinants for UIA were female sex (OR 2.00, 95%CI 1.45-2.77, p < 0.001), hypertension (OR 1.48, 95%CI 1.08-2.04, p = 0.015), smoking (OR 1.41, 95%CI 1.03-1.95, p = 0.036), and BMI (OR 0.95, 95%CI 0.91-0.98, p = 0.004). Among subjects with UIA, 9.4% with a BMI > 25 had multiple aneurysms, compared to 21.6% with BMI ≤ 25 (p = 0.012). This study suggests that a high BMI exhibits a protective effect on UIA incidence and the development of multiple aneurysms. Additionally, the data confirms established risk factors for UIA development, such as female sex, hypertension, and smoking.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease. 手术血管重建对成人莫亚莫亚病血管周围扩大空间消退的影响
IF 3.8 2区 医学
Translational Stroke Research Pub Date : 2024-10-08 DOI: 10.1007/s12975-024-01303-3
Shusuke Yamamoto, Takuya Akai, Daina Kashiwazaki, Kunitaka Maruyama, Emiko Hori, Naoki Akioka, Kyo Noguchi, Satoshi Kuroda
{"title":"Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.","authors":"Shusuke Yamamoto, Takuya Akai, Daina Kashiwazaki, Kunitaka Maruyama, Emiko Hori, Naoki Akioka, Kyo Noguchi, Satoshi Kuroda","doi":"10.1007/s12975-024-01303-3","DOIUrl":"https://doi.org/10.1007/s12975-024-01303-3","url":null,"abstract":"<p><p>Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3 months and 2 years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3 months and 2 years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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