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Intra-cisterna-magna bevacizumab injection (ICM-BI) reproduces pathological alterations of cerebral small vessel diseases. 蝶窦内注射贝伐珠单抗(ICM-BI)可重现脑小血管疾病的病理改变。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-25 DOI: 10.1177/0271678X241295856
Xinmei Kang, Xiaotao Su, Tiemei Li, Shisi Wang, Huipeng Huang, Yuxin Liu, Chunyi Li, Xiaohui Deng, Mengyan Hu, Tingting Lu, Lei Wei, Wei Cai, Zhengqi Lu

General modeling strategies for sporadic cerebral small blood vessel diseases (CSVDs) include limiting blood stream in large blood vessels and inducing systemic hypertension, in which small blood vessel deficit is either a secondary or concomitant pathology. In the current study, we introduce that intra-cisterna-magna Bevacizumab injection (ICM-BI) directly causes cerebral small blood vessel injury by neutralizing VEGF-A, the indispensable growth factor for angiogenesis. ICM-BI reproduces neuro-functional impairment, tight junction loss, cerebral micro-bleeds (CMBs), amyloid peptide accumulation, neuronal injury, white matter loss, and glial cell activation, which are common manifestations of sporadic CSVDs. Compared with existing CSVD models, small blood vessel injury is more prominent in the ICM-BI brain. Moreover, no significant alteration in large blood vessels or peripheral organs after ICM-BI is recorded. We thus propose that ICM-BI is a neat, economic and applicable methodology to establish murine sporadic CSVD model.

散发性脑小血管疾病(CSVDs)的一般建模策略包括限制大血管血流和诱发全身性高血压,其中小血管缺损是继发或并发病症。在本研究中,我们介绍了蝶窦内注射贝伐珠单抗(ICM-BI)通过中和血管生成不可或缺的生长因子 VEGF-A 直接导致脑小血管损伤。ICM-BI 重现了散发性 CSVD 常见的神经功能损伤、紧密连接缺失、脑微出血(CMB)、淀粉样肽积累、神经元损伤、白质丢失和神经胶质细胞活化。与现有的 CSVD 模型相比,ICM-BI 大脑中的小血管损伤更为突出。此外,ICM-BI 后大血管或外周器官没有明显变化。因此,我们认为 ICM-BI 是建立小鼠散发性 CSVD 模型的一种简便、经济和适用的方法。
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引用次数: 0
Aging affects the mouse brain in a region-specific manner. 衰老以特定区域的方式影响小鼠大脑。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-18 DOI: 10.1177/0271678X241289780
Ling Cai, Yueman Zhang, Yuxi Zhou, Xin Wang

Aging-related cognitive decline is emerging as a health concern during the aging process of the global population. Hahn and colleagues found that glial aging was particularly accelerated in white matter compared to cortical regions. Specialized neuronal populations showed region-specific changes in gene expression. Acute dietary restriction triggers a reprogramming of genes associated with the circadian clock in glial cells, whereas injections of young mouse plasma selectively reverse age-related expression patterns. The discovery of region-specific aging could enhance our understanding of the aging process and offer new possibilities for innovative treatment strategies and interventions for cognitive impairments related to aging.

与衰老相关的认知能力下降正在成为全球人口老龄化过程中的一个健康问题。Hahn 及其同事发现,与皮质区域相比,白质区域的神经胶质老化尤其加速。特化的神经元群在基因表达方面出现了区域特异性变化。急性饮食限制会引发神经胶质细胞中与昼夜节律相关基因的重编程,而注射年轻小鼠血浆则会选择性地逆转与年龄相关的表达模式。区域特异性衰老的发现可以加深我们对衰老过程的理解,并为创新治疗策略和干预与衰老相关的认知障碍提供新的可能性。
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引用次数: 0
Statistical non-independence of brain metabolite concentrations whether normalized to creatine or water. 无论是以肌酸还是以水为标准,大脑代谢物浓度在统计上都不具有独立性。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-18 DOI: 10.1177/0271678X241290018
Richard J Maddock

1H-MRS investigators studying brain metabolite concentrations often attribute biological significance to correlations between calculated metabolite values within the same voxel. A recent report in this journal provides a valuable perspective on how statistical non-independence of such values can undermine biological interpretations of their correlations. However, careful examination of this issue suggests their critical analysis does not go far enough. Hong et al. claim that appropriate water normalization, unlike creatine normalization, eliminates the problem of spurious correlation. Both logical and empirical considerations show this is not the case. Correlations between water-normalized metabolite values are also prone to substantial spurious correlations.

研究大脑代谢物浓度的 1H-MRS 研究人员经常将同一体素内代谢物计算值之间的相关性归因于生物学意义。本刊最近的一篇报道提供了一个有价值的视角,揭示了这些值在统计学上的非独立性如何会破坏对其相关性的生物学解释。然而,对这一问题的仔细研究表明,他们的批判性分析还不够深入。Hong 等人声称,与肌酸正常化不同,适当的水分正常化可以消除虚假相关性问题。逻辑和经验都表明事实并非如此。水归一化代谢物值之间的相关性也容易产生大量的假相关。
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引用次数: 0
More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis. 有症状的颅内动脉粥样硬化性狭窄患者脑小血管病变较严重,且脑外膜侧支较差。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-18 DOI: 10.1177/0271678X241292537
Yuying Liu, Shuang Li, Xuan Tian, Jill Abrigo, Bonnie Yk Lam, Jize Wei, Lina Zheng, Yu Liu, Ziqi Li, Tingjun Liang, Bonaventure Ym Ip, Thomas W Leung, Xinyi Leng

We investigated the association between cerebral small vessel disease (CSVD) and ipsilateral leptomeningeal collateral (LMC) status in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). In 108 patients with 50-99% symptomatic intracranial internal carotid artery or M1 middle cerebral artery stenosis, 4 CSVD imaging markers (lacunes, cerebral microbleeds, enlarged perivascular spaces [EPVSs], and white matter hyperintensities [WMHs]) were assessed in MRI. Score of 0 or 1 was assigned to each marker and added up as a summary CSVD score (ranging 0-4) to reflect an overall CSVD burden. Ipsilateral LMC status was assessed by determining the laterality of distal vessels in anterior and posterior cerebral artery territories on CT angiography. Moderate-to-severe EPVSs (adjusted odds ratio [aOR] = 4.15; p = 0.031) and WMHs (aOR = 5.90; p = 0.010), and higher summary CSVD score (aOR = 1.66; p = 0.030) were independently associated with poor LMCs. There was significant interaction between stenosis percentage in sICAS and summary CSVD score on poor LMCs (p = 0.022 for interaction), when higher CSVD score was significantly associated with poor LMCs in patients with severe sICAS (aOR = 2.84; p = 0.011) but not in those with moderate sICAS. The findings indicated possibly adverse effect of CSVD on the recruitment or development of LMCs in sICAS patients, especially in patients with severe sICAS.

我们研究了无症状颅内动脉粥样硬化性狭窄(sICAS)患者的脑小血管疾病(CSVD)与同侧脑侧索(LMC)状态之间的关系。在 108 例 50-99% 的无症状颅内颈内动脉或 M1 大脑中动脉狭窄患者中,对 4 种 CSVD 影像标记(裂隙、脑微出血、血管周围间隙增大 [EPVSs] 和白质增厚 [WMHs])进行了磁共振成像评估。每个标记的得分均为 0 或 1,然后加总为 CSVD 总分(0-4 分不等),以反映 CSVD 的总体负担。同侧 LMC 状态通过 CT 血管造影确定大脑前后动脉区域远端血管的侧向性来评估。中度至重度 EPVS(调整后比值比 [aOR] = 4.15;p = 0.031)和 WMHs(aOR = 5.90;p = 0.010)以及较高的 CSVD 总分(aOR = 1.66;p = 0.030)与 LMC 较差独立相关。sICAS 狭窄百分比与 CSVD 简要评分之间存在明显的交互作用(交互作用 p = 0.022),在重度 sICAS 患者中,较高的 CSVD 评分与 LMCs 差异显著相关(aOR = 2.84;p = 0.011),而在中度 sICAS 患者中则不相关。研究结果表明,CSVD可能会对sICAS患者LMCs的招募或发展产生不利影响,尤其是在重度sICAS患者中。
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引用次数: 0
Somatosensory migraine auras evoked by bihemispheric cortical spreading depression events in human parietal cortex. 人类顶叶皮层双半球皮质扩张性抑郁事件诱发的躯体感觉性偏头痛光环。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-13 DOI: 10.1177/0271678X241290606
Cedric Gollion, Rune H Christensen, Håkan Ashina, Haidar M Al-Khazali, Patrick M Fisher, Faisal Mohammad Amin, Martin Lauritzen, Messoud Ashina

Cortical spreading depression (CSD) is associated with pronounced alterations in cerebral blood flow. These alterations can be captured using high-field functional magnetic resonance imaging (fMRI). While compelling clinical and experimental data suggest that CSD is involved in the pathogenesis of migraine aura, the mechanistic intricacies remain poorly understood. Here, we use visual stimulus-induced blood oxygen level-dependent (BOLD) fMRI responses to characterize spatiotemporal alterations in cerebral blood flow during spontaneous attacks with migraine aura. Six adult participants diagnosed with migraine with aura underwent BOLD fMRI scans with a visual stimulation paradigm, consisting of flickering checkerboard stimulation. Our results revealed that auras with somatosensory symptoms corresponded with bilateral alterations of stimulus-induced BOLD responses in the somatosensory cortex, exhibiting anterior-to-posterior propagation and absence of antecedent occipital abnormalities. These altered stimulus-induced BOLD responses were bilateral, despite a unilateral manifestation of aura symptoms, and had no relationship with positive or negative aura symptoms. The bilateral abnormalities in stimulus-induced BOLD responses completes our current knowledge on migraine aura.

皮层扩张抑制(CSD)与脑血流的明显改变有关。这些改变可以通过高场功能磁共振成像(fMRI)捕捉到。尽管令人信服的临床和实验数据表明 CSD 与偏头痛先兆的发病机制有关,但人们对其复杂的机理仍然知之甚少。在这里,我们利用视觉刺激诱导的血氧水平依赖性(BOLD)fMRI反应来描述偏头痛先兆自发发作时脑血流的时空变化。六名被诊断为先兆偏头痛的成年患者接受了由闪烁棋盘刺激组成的视觉刺激范式的BOLD fMRI扫描。我们的研究结果表明,伴有躯体感觉症状的先兆与躯体感觉皮层的双侧刺激诱导BOLD反应改变相对应,表现出前后传播,且没有先兆枕叶异常。尽管先兆症状表现为单侧,但这些刺激诱导的BOLD反应改变是双侧的,与阳性或阴性先兆症状没有关系。刺激诱导的BOLD反应的双侧异常完善了我们目前对偏头痛先兆的认识。
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引用次数: 0
Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen. 静脉注射缪斯细胞可通过脾脏的免疫调节改善脑缺血的预后。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-13 DOI: 10.1177/0271678X241290363
Yuya Kato, Daiki Aburakawa, Ryosuke Tashiro, Yuan Zhou, Sherif Rashad, Hidenori Endo, Teiji Tominaga, Kuniyasu Niizuma

Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.

缺血性中风是全球致残和致死的主要原因。干细胞疗法正在成为促进中风后康复的前沿疗法,其中缪斯细胞--多能干细胞的亚类--显示出巨大的前景。Muse细胞不仅在细胞替代方面具有潜力,而且在调节脑梗塞后的免疫反应方面也发挥着重要作用。在本研究中,我们通过远端大脑中动脉闭塞诱发小鼠中风后,静脉注射 Muse 细胞。我们评估了诱导中风两周后的运动结果、脾细胞群、细胞因子谱和基因表达。此外,我们还比较了切除脾脏的小鼠和接受收养脾细胞转移的小鼠的疗效,以确定脾脏对疗效的具体影响。我们的研究结果表明,Muse 细胞疗法能促进运动功能的恢复,而在没有脾脏的情况下,这种效果会大打折扣。接受治疗的小鼠的脾脏表现出中性粒细胞计数的变化、细胞因子活性的增加以及与蛋白质折叠相关的基因表达的显著上升。这些发现肯定了Muse细胞在中风后治疗策略中的潜在疗效,其疗效至少部分归因于涉及脾脏的免疫调节途径。
{"title":"Intravenous administration of muse cells improves cerebral ischemia outcome via immunomodulation in the spleen.","authors":"Yuya Kato, Daiki Aburakawa, Ryosuke Tashiro, Yuan Zhou, Sherif Rashad, Hidenori Endo, Teiji Tominaga, Kuniyasu Niizuma","doi":"10.1177/0271678X241290363","DOIUrl":"10.1177/0271678X241290363","url":null,"abstract":"<p><p>Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241290363"},"PeriodicalIF":5.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
A support vector machine-based approach to guide the selection of a pseudo-reference region for brain PET quantification. 基于支持向量机的方法,用于指导脑 PET 定量伪参考区域的选择。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-13 DOI: 10.1177/0271678X241290912
Chunmeng Tang, Greet Vanderlinden, Gwen Schroyen, Sabine Deprez, Koen Van Laere, Michel Koole

A Support Vector Machine (SVM) based approach was developed to identify a pseudo-reference region for brain PET scans with the aim of reducing interscan and intersubject variability. By training a binary linear SVM classifier with PET datasets from two different groups, potential pseudo-reference regions were identified by considering their regional average or total contribution to the classification score. This approach was evaluated in three cohorts with different brain PET tracers: (1) 11C-PiB PET scans of Alzheimer's disease (AD) patients and age-matched controls (OC); (2) baseline and blocking scans of an 11C-UCB-J PET occupancy study; and (3) 18F-DPA-714 PET scans for healthy controls (HC) and chemo-treated women with breast cancer (BC). In the first cohort, cerebellum, brainstem, and subcortical white matter were confirmed as pseudo-reference regions. The same regions were identified for the second cohort using either the VT maps or the SUV images. In the third cohort, cerebellum and brainstem were identified as pseudo-reference regions, alongside subcortical white matter and temporal cortex. In addition, the SVM-based approach demonstrated robust performance even with a reduced number of subjects, therefore confirming its applicability in identifying pseudo-reference regions without a priori assumptions and with only limited data across different PET tracers.

我们开发了一种基于支持向量机(SVM)的方法来识别脑 PET 扫描的伪参考区域,目的是减少扫描间和受试者间的变异性。通过对来自两个不同组的 PET 数据集进行二元线性 SVM 分类器训练,考虑其对分类得分的区域平均或总贡献,确定潜在的伪参考区域。该方法在使用不同脑 PET 示踪剂的三个队列中进行了评估:(1) 阿尔茨海默病(AD)患者和年龄匹配对照(OC)的 11C-PiB PET 扫描;(2) 11C-UCB-J PET 占位研究的基线和阻断扫描;(3) 健康对照(HC)和化疗妇女乳腺癌(BC)的 18F-DPA-714 PET 扫描。在第一个队列中,小脑、脑干和皮层下白质被确认为伪参考区域。第二组患者也使用 VT 图或 SUV 图像确定了相同的区域。在第三个队列中,小脑和脑干以及皮层下白质和颞叶皮质被确定为伪参考区域。此外,即使受试者人数减少,基于 SVM 的方法也能表现出稳健的性能,因此证实了该方法适用于在没有先验假设的情况下识别伪参考区域,而且只需跨不同 PET 示踪剂的有限数据。
{"title":"A support vector machine-based approach to guide the selection of a pseudo-reference region for brain PET quantification.","authors":"Chunmeng Tang, Greet Vanderlinden, Gwen Schroyen, Sabine Deprez, Koen Van Laere, Michel Koole","doi":"10.1177/0271678X241290912","DOIUrl":"10.1177/0271678X241290912","url":null,"abstract":"<p><p>A Support Vector Machine (SVM) based approach was developed to identify a pseudo-reference region for brain PET scans with the aim of reducing interscan and intersubject variability. By training a binary linear SVM classifier with PET datasets from two different groups, potential pseudo-reference regions were identified by considering their regional average or total contribution to the classification score. This approach was evaluated in three cohorts with different brain PET tracers: (1) <sup>11</sup>C-PiB PET scans of Alzheimer's disease (AD) patients and age-matched controls (OC); (2) baseline and blocking scans of an <sup>11</sup>C-UCB-J PET occupancy study; and (3) <sup>18</sup>F-DPA-714 PET scans for healthy controls (HC) and chemo-treated women with breast cancer (BC). In the first cohort, cerebellum, brainstem, and subcortical white matter were confirmed as pseudo-reference regions. The same regions were identified for the second cohort using either the V<sub>T</sub> maps or the SUV images. In the third cohort, cerebellum and brainstem were identified as pseudo-reference regions, alongside subcortical white matter and temporal cortex. In addition, the SVM-based approach demonstrated robust performance even with a reduced number of subjects, therefore confirming its applicability in identifying pseudo-reference regions without a priori assumptions and with only limited data across different PET tracers.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241290912"},"PeriodicalIF":5.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 0
Medin, a link between vascular pathology and dementia? 梅丁,血管病理学与痴呆症之间的联系?
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-07 DOI: 10.1177/0271678X241289772
Ilse S Altenburg, Nina G Smets, Gustav J Strijkers, Erik Ntp Bakker

Medin is a protein fragment derived from milk fat globule epidermal growth factor VIII (MFG-E8). Medin aggregates are present in the vessel wall of most subjects over 50 years of age. In this narrative review, we focus on the consequences of medin aggregation in relation to the development of dementia. Recent literature revealed medin as biomarker for dementia in CSF, specifically of a vascular subtype. Preclinical work showed that medin is associated with aging-related cerebral vascular dysfunction, vascular stiffening, hypertension, and. vascular amyloid β deposition. These findings position medin as a potential mechanistic link between aging, vascular pathology and dementia.

Medin 是一种从牛奶脂肪球表皮生长因子 VIII(MFG-E8)中提取的蛋白质片段。大多数 50 岁以上的人血管壁中都存在 Medin 聚集。在这篇叙述性综述中,我们将重点关注髓磷脂聚集与痴呆症发展的关系。最近的文献显示,medin 是脑脊液中痴呆症的生物标志物,特别是血管亚型痴呆症。临床前研究表明,medin 与衰老相关的脑血管功能障碍、血管硬化、高血压和血管淀粉样蛋白 β 沉积有关。这些研究结果表明,medin 是衰老、血管病理学和痴呆症之间的潜在机理联系。
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引用次数: 0
Reliable infarction of the middle cerebral artery territory in C57BL/6 mice using pterygopalatine artery ligation and filament optimization - The PURE-MCAo model. 利用翼腭动脉结扎和细丝优化技术对 C57BL/6 小鼠大脑中动脉区域进行可靠的梗塞治疗--PURE-MCAo 模型。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-07 DOI: 10.1177/0271678X241281841
Sodai Yoshimura, Maximilian Dorok, Uta Mamrak, Antonia Wehn, Eva Krestel, Igor Khalin, Nikolaus Plesnila

Current techniques for inducing intraluminal filamentous middle cerebral artery occlusion (fMCAo) in mice produce highly variable results and often cause additional infarcts in the posterior cerebral artery (PCA) territory. The aim of the current study was to develop a novel procedure to overcome these shortcomings. Male C57BL/6 mice were subjected to 60 min of fMCAo with cerebral blood flow monitored by laser Doppler flowmetry. The influence of the length of the occlusion filament coating and the combination of common carotid artery (CCA) or pterygopalatine artery (PPA) ligation on lesion volume and functional outcome 24 h after reperfusion was evaluated. The use of appropriate filament and PPA ligation while maintaining CCA perfusion prevented the development of infarcts in the PCA area, resulted in pure MCA infarcts (68.3 ± 14.5 mm3) and reduced the variability of infarct volumes by more than half (from 26-38% to 14% standard deviation/mean). Using an improved fMCAo procedure, we were able to produce PCA area-unaffected reproducible (PURE) infarcts exclusively in the MCA territory. Thus PURE-MCAo reduced outcome variability by more than 50%. Our results may thus help to reduce the number of animals in preclinical stroke research and to increase the reproducibility of the fMCAo model.

目前诱导小鼠腔内丝状大脑中动脉闭塞(fMCAo)的技术产生的结果差异很大,而且往往会造成大脑后动脉(PCA)区域的额外梗死。本研究旨在开发一种新的程序来克服这些缺点。对雄性 C57BL/6 小鼠进行 60 分钟 fMCAo,并通过激光多普勒血流测量仪监测脑血流。评估了闭塞丝膜的长度以及颈总动脉(CCA)或翼腭动脉(PPA)结扎的组合对病变体积和再灌注 24 小时后功能结果的影响。在维持CCA灌注的同时,使用适当的丝状动脉和PPA结扎可防止PCA区域发生梗死,导致纯MCA梗死(68.3 ± 14.5 mm3),并将梗死体积的变异性降低一半以上(从26-38%降至14%的标准偏差/平均值)。利用改进的 fMCAo 程序,我们能够完全在 MCA 区域产生 PCA 区域未受影响的可重复梗死(PURE)。因此,PURE-MCAo 将结果变异性降低了 50% 以上。因此,我们的研究结果可能有助于减少临床前中风研究中的动物数量,并提高 fMCAo 模型的可重复性。
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引用次数: 0
Cerebral blood flow from arterial spin labeling as an imaging biomarker of outcome after endovascular therapy for ischemic stroke. 动脉自旋标记的脑血流作为缺血性中风血管内治疗后疗效的成像生物标志物。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-10-04 DOI: 10.1177/0271678X241267066
Moritz R Hernandez Petzsche, Johannes Bürkle, Gabriel Hoffmann, Claus Zimmer, Sebastian Rühling, Julian Schwarting, Silke Wunderlich, Christian Maegerlein, Tobias Boeckh-Behrens, Stefan Kaczmarz, Maria Berndt-Mück, Nico Sollmann

Arterial spin labeling (ASL) is a contrast agent-free magnetic resonance imaging (MRI) technique to measure cerebral blood flow (CBF). We sought to investigate effects of CBF within the infarct on outcome and risk of hemorrhagic transformation (HT). In 111 patients (median age: 74 years, 50 men) who had undergone mechanical thrombectomy (MT) for ischemic stroke of the anterior circulation (median interval: 4 days between MT and MRI), post-stroke %CBF difference from pseudo-continuous ASL was calculated within the diffusion-weighted imaging (DWI)-positive infarct territory following lesion segmentation in relationship to the unaffected contralateral side. Functional independence was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days post-stroke. %CBF difference, pre-stroke mRS, and infarct volume were independently associated with functional independence in a multivariate regression model. %CBF difference was comparable between patients with and without HT. A subcohort of 10 patients with decreased infarct-CBF despite expanded Treatment in Cerebral Infarction (eTICI) 2c or 3 recanalization was identified (likely related to the no-reflow phenomenon). Outcome was significantly worse in this group compared to the remaining cohort. In conclusion, ASL-derived %CBF difference from the DWI-positive infarct territory independently predicted functional independence, but %CBF difference was not significantly associated with an increased risk of HT.

动脉自旋标记(ASL)是一种测量脑血流(CBF)的不含造影剂的磁共振成像(MRI)技术。我们试图研究脑梗塞内的 CBF 对预后和出血转化(HT)风险的影响。在 111 例因前循环缺血性中风而接受了机械性血栓切除术(MT)的患者(中位年龄:74 岁,男性 50 例)中(MT 和 MRI 之间的中位间隔:4 天),在病灶分割后计算了与未受影响的对侧相比,弥散加权成像(DWI)阳性梗死区内的假连续 ASL 中的中风后百分比 CBF 差异。卒中后 90 天的改良 Rankin 量表(mRS)为 0-2,即为功能独立。在多变量回归模型中,%CBF 差值、卒中前 mRS 和梗死体积与功能独立性独立相关。有高密度脂蛋白胆固醇血症和无高密度脂蛋白胆固醇血症的患者之间的百分比CBF差值相当。在脑梗死扩大治疗(eTICI)2c 或 3 级再通后,仍有 10 例患者的梗死-CBF 下降(可能与无回流现象有关)。与其他队列相比,该组患者的预后明显较差。总之,从 DWI 阳性梗死区域得出的 ASL 导出百分比 CBF 差异可独立预测功能独立性,但百分比 CBF 差异与 HT 风险增加无明显关联。
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引用次数: 0
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Journal of Cerebral Blood Flow and Metabolism
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