Pub Date : 2024-10-25DOI: 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.
{"title":"Intra-cisterna-magna bevacizumab injection (ICM-BI) reproduces pathological alterations of cerebral small vessel diseases.","authors":"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","doi":"10.1177/0271678X241295856","DOIUrl":"10.1177/0271678X241295856","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241295856"},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501175","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}
Pub Date : 2024-10-18DOI: 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.
{"title":"Aging affects the mouse brain in a region-specific manner.","authors":"Ling Cai, Yueman Zhang, Yuxi Zhou, Xin Wang","doi":"10.1177/0271678X241289780","DOIUrl":"10.1177/0271678X241289780","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241289780"},"PeriodicalIF":5.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466522","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}
Pub Date : 2024-10-18DOI: 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.
{"title":"Statistical non-independence of brain metabolite concentrations whether normalized to creatine or water.","authors":"Richard J Maddock","doi":"10.1177/0271678X241290018","DOIUrl":"10.1177/0271678X241290018","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241290018"},"PeriodicalIF":5.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466526","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}
Pub Date : 2024-10-18DOI: 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.
{"title":"More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis.","authors":"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","doi":"10.1177/0271678X241292537","DOIUrl":"10.1177/0271678X241292537","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241292537"},"PeriodicalIF":5.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466524","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}
Pub Date : 2024-10-13DOI: 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.
{"title":"Somatosensory migraine auras evoked by bihemispheric cortical spreading depression events in human parietal cortex.","authors":"Cedric Gollion, Rune H Christensen, Håkan Ashina, Haidar M Al-Khazali, Patrick M Fisher, Faisal Mohammad Amin, Martin Lauritzen, Messoud Ashina","doi":"10.1177/0271678X241290606","DOIUrl":"10.1177/0271678X241290606","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241290606"},"PeriodicalIF":5.4,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466525","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}
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.
{"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}
Pub Date : 2024-10-13DOI: 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}
Pub Date : 2024-10-07DOI: 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.
{"title":"Medin, a link between vascular pathology and dementia?","authors":"Ilse S Altenburg, Nina G Smets, Gustav J Strijkers, Erik Ntp Bakker","doi":"10.1177/0271678X241289772","DOIUrl":"10.1177/0271678X241289772","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241289772"},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380952","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}
Pub Date : 2024-10-07DOI: 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.
{"title":"Reliable infarction of the middle cerebral artery territory in C57BL/6 mice using pterygopalatine artery ligation and filament optimization - The PURE-MCAo model.","authors":"Sodai Yoshimura, Maximilian Dorok, Uta Mamrak, Antonia Wehn, Eva Krestel, Igor Khalin, Nikolaus Plesnila","doi":"10.1177/0271678X241281841","DOIUrl":"10.1177/0271678X241281841","url":null,"abstract":"<p><p>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 mm<sup>3</sup>) 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 <u>P</u>CA area-<u>u</u>naffected <u>re</u>producible (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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241281841"},"PeriodicalIF":5.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380953","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}
Pub Date : 2024-10-04DOI: 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.
{"title":"Cerebral blood flow from arterial spin labeling as an imaging biomarker of outcome after endovascular therapy for ischemic stroke.","authors":"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","doi":"10.1177/0271678X241267066","DOIUrl":"10.1177/0271678X241267066","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241267066"},"PeriodicalIF":5.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371955","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}