Fluids and Barriers of the CNS最新文献

{"title":"The heart-brain crosstalk in age related cardiovascular and neurodegenerative diseases.","authors":"Muhammad Ahmad Fahim, Yao Yao, Srinivas M Tipparaju, Wanling Xuan","doi":"10.1186/s12987-025-00700-6","DOIUrl":"https://doi.org/10.1186/s12987-025-00700-6","url":null,"abstract":"<p><p>Aging is a major risk factor for both cardiovascular and neurodegenerative diseases. The bidirectional communication between the heart and brain, commonly referred to as heart-brain crosstalk, is increasingly disrupted with age. In this review, we summarize current evidence linking cardiovascular and neurodegenerative disorders, particularly in the context of aging. We also discuss the underlying mechanisms responsible for the heart-brain crosstalk, including blood-brain barrier breakdown, vascular dysfunction, nervous system alterations, inflammation, and endocrine dysregulation, which may explain the frequent co-occurrence of dysfunction in both organs during aging. Understanding these interconnections provides critical insights into the pathophysiology of age-related diseases and highlights potential therapeutic targets to preserve both heart and brain health in the aging population.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"89"},"PeriodicalIF":6.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948434","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":"Focused ultrasound-mediated temozolomide delivery into intact blood-brain barrier tissue improves survival in patient-derived xenograft model of glioblastoma.","authors":"Jaewoo Shin, Jin-Kyoung Shim, Chanho Kong, Younghee Seo, Sangheon Han, Seok-Gu Kang, Won Seok Chang","doi":"10.1186/s12987-025-00695-0","DOIUrl":"https://doi.org/10.1186/s12987-025-00695-0","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"87"},"PeriodicalIF":6.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948421","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":"Endothelial mitochondria in the blood-brain barrier.","authors":"Yunwei Shao, Lingling Mai, Ruogu Qiao, Yi Liang, Yuying Jiao, Judith Homburg, Zhenfu Jiang, Laiyu Song","doi":"10.1186/s12987-025-00699-w","DOIUrl":"https://doi.org/10.1186/s12987-025-00699-w","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a highly selective interface between the peripheral circulation and the central nervous system (CNS), crucial for maintaining brain homeostasis. Disruptions to the BBB, such as increased permeability or structural damage, can lead to neurological damage. Mitochondria, the primary energy producers within endothelial cells, play a key role in the function of the BBB by maintaining its integrity and low permeability. This review first outlines the structural components of the BBB, then examines the role of mitochondria in endothelial cells under physiological conditions. We further focus on alterations in mitochondrial function during pathological states, discussing their impact on BBB stability. Briefly, this review explores the involvement of mitochondria in BBB endothelial cells in both physiological processes and the pathological progression of neurological diseases, while proposing potential therapeutic directions for treating CNS disorders.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"88"},"PeriodicalIF":6.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948387","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":"High-affinity transferrin receptor binding improves brain delivery of bispecific antibodies at tracer dose.","authors":"Gillian Bonvicini, Sunitha Singh, Lisa Sandersjöö, Tiffany Dallas, Eva Schlein, Amelia D Dahlén, Sara Lopes van den Broek, Dag Sehlin, Ken G Andersson, Stina Syvänen","doi":"10.1186/s12987-025-00693-2","DOIUrl":"https://doi.org/10.1186/s12987-025-00693-2","url":null,"abstract":"<p><strong>Background: </strong>Transferrin receptor (TfR)-mediated transcytosis is a well-established method for delivering biologic therapeutics and diagnostics to the brain. Although moderate affinity towards TfR is beneficial for TfR-mediated brain delivery at therapeutic doses, emerging evidence has indicated that high TfR affinity may be more beneficial at tracer doses. With the development of antibody-based PET radioligands for neurodegenerative diseases, such as Alzheimer's disease, understanding the pharmacokinetics of TfR-binders at tracer dose is essential. Thus, this study aimed to evaluate the effect of TfR affinity on brain uptake at a tracer dose in both wild-type (WT) and amyloid-beta (Aβ) pathology presenting mice and to demonstrate the usability of TfR-mediated brain delivery of immunoPET diagnostic radioligands to visualize intrabrain Aβ pathology in vivo.</p><p><strong>Methods: </strong>Three different affinity variants of anti-mouse TfR-binding antibody 8D3, engineered by alanine point mutations, were selected. Bispecific antibodies were designed with knob-into-hole technology with one arm targeting TfR (8D3) and the other arm targeting human Aβ (bapineuzumab). Antibody affinities were measured in an in vitro cell assay. In vivo pharmacokinetic analyses of radioiodinated bispecific antibodies and bapineuzumab in brain, blood and peripheral organs were performed over 7 days post-injection in WT mice and a model of Aβ pathology (App^NL-G-F). The strongest TfR affinity bispecific antibody was also evaluated as a positron emission tomography (PET) radioligand for detecting Aβ pathology in WT and App^NL-G-F mice.</p><p><strong>Results: </strong>The three bispecific antibodies bound to TfR with affinities of 10 nM, 20 nM and 240 nM. Independent of genotype, stronger TfR-affinity resulted in higher initial brain uptake. The two higher-affinity bispecific antibodies behaved similarly and differentiated between WT and App^NL-G-F mice earlier than the lowest affinity variant. Finally, the 10 nM bispecific antibody was able to clearly differentiate between WT and App^NL-G-F mice when used as a PET radioligand.</p><p><strong>Conclusion: </strong>This study supports the hypothesis that stronger TfR affinity enhances brain uptake at a tracer dose. With the more effective detection of Aβ pathology, stronger TfR affinity is a crucial design feature for future bispecific immunoPET radioligands for intrabrain targets via TfR-mediated transcytosis.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"86"},"PeriodicalIF":6.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948466","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":"Bridging regional neurovascular unit heterogeneity and cognitive function: a review.","authors":"Amalia Tsintzou, Roseline Poirier, Rania Harati, Almira Kustubayeva, Clemence Disdier, Rifat Hamoudi, Aloïse Mabondzo","doi":"10.1186/s12987-025-00697-y","DOIUrl":"https://doi.org/10.1186/s12987-025-00697-y","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a critical central nervous system interface that tightly regulates the exchange of substances between the blood circulation and the brain parenchyma. The BBB, glia, mural cells and neurons form the neurovascular unit (NVU), which modulates cerebral homeostasis. Traditionally considered a uniform and selective barrier, emerging research has unveiled significant heterogeneity in BBB properties across various brain structures. This review synthesizes current knowledge of the heterogeneity of the NVU elements of different brain structures. The structural and functional differences of the endothelial cells, glial cells, and neurons of different brain structures are pinpointed. Finally, BBB heterogeneity and its link to cognition in physiology and pathology are discussed. Understanding such relationships could help effectively target and cure neurological diseases.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"85"},"PeriodicalIF":6.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948463","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":"Sleep reduces CSF concentrations of beta-amyloid and tau: a randomized crossover study in healthy adults.","authors":"Tim Lyckenvik, Martin Olsson, My Forsberg, Pontus Wasling, Henrik Zetterberg, Jan Hedner, Eric Hanse","doi":"10.1186/s12987-025-00698-x","DOIUrl":"10.1186/s12987-025-00698-x","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"84"},"PeriodicalIF":6.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882508","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":"Subcortical and white matter alterations in canine ventriculomegaly: an observational volumetric and voxel-based-morphometry study.","authors":"Tom Cornelius Cyriacks, Martin J Schmidt, Eberhard Ludewig, Johannes Boltze, Robert Dahnke, Simone A Fietz, Björn Nitzsche","doi":"10.1186/s12987-025-00696-z","DOIUrl":"10.1186/s12987-025-00696-z","url":null,"abstract":"<p><strong>Objective: </strong>Ventriculomegaly and hydrocephalus are frequently found during routine clinical imaging, and hydrocephalus in dogs has been shown to alter brain tissue. Although approaches exist to differentiate canine hydrocephalus from ventriculomegaly, information about brain tissue alterations in dogs with ventriculomegaly is lacking. In this observational study, we focused on ventriculomegaly and examined the cerebral anatomical adaptations that accommodate the increased ventricular volume.</p><p><strong>Methods: </strong>95 neuroradiological normal diagnosed dogs of different breeds were divided into the two groups, ventriculomegaly and control, according to morphological criteria and ventricle-brain-indices as determined by ratio of brain and lateral ventricle wide. Brain volumetry and voxel-based-morphometry (VBM) were conducted using automatic procedures employing the Statistical Parametric Mapping software and a canine brain atlas.</p><p><strong>Results: </strong>Significant alterations in cingulate cortex, caudate nucleus, thalamus, hippocampus, geniculate body as well as corpus callosum were observed in dogs of the ventriculomegaly group by both volumetry and VBM. Interestingly, ventriculomegaly affected only lateral ventricles, the 3rd ventricle, and the mesencephalic aqueduct but not the 4th ventricle.</p><p><strong>Discussion: </strong>A clear distinction between canine hydrocephalus and ventriculomegaly remains difficult and recent research suggests parallels between both. Advances in automated segmentation methods and voxel-based morphometry applicable to canine magnetic resonance imaging offer the opportunity to comprehensively assess structural abnormalities. In addition, clinical assessments are required to investigate the impact of ventriculomegaly on cognitive function and behavior in further studies.</p><p><strong>Conclusion: </strong>We propose the use of a lower ventricle-brain-index threshold of ≥ 0.5 to include all ventricle-associated tissue alterations with potential clinical manifestation.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"83"},"PeriodicalIF":6.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872201","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":"Advection versus diffusion in brain ventricular transport.","authors":"Halvor Herlyng, Ada J Ellingsrud, Miroslav Kuchta, Inyoung Jeong, Marie E Rognes, Nathalie Jurisch-Yaksi","doi":"10.1186/s12987-025-00692-3","DOIUrl":"10.1186/s12987-025-00692-3","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) is integral to brain function. CSF provides mechanical support for the brain and helps distribute nutrients, neurotransmitters and metabolites throughout the central nervous system. CSF flow is driven by several processes, including the beating of motile cilia located on the walls of the brain ventricles. Despite the physiological importance of CSF, the underlying mechanisms of CSF flow and solute transport in the brain ventricles remain to be comprehensively resolved. This study analyzes and evaluates specifically the role of motile cilia in CSF flow and transport. We developed finite element methods for modeling flow and transport using the geometry of embryonic zebrafish brain ventricles, for which we have detailed knowledge of cilia properties and CSF motion. The computational model is validated by in vivo experiments that monitor transport of a photoconvertible protein secreted in the brain ventricles. Our results show that while cilia contribute to advection of large particles, diffusion plays a significant role in the transport of small solutes. We also demonstrate how cilia location and the geometry of the ventricular system impact solute distribution. Altogether, this work presents a computational framework that can be applied to other ventricular systems, together with new concepts of how molecules are transported within the brain and its ventricles.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"82"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845074","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":"Mixed-dimensional fluid-structure interaction simulations reveal key mechanisms of cerebrospinal fluid dynamics in the spinal canal.","authors":"Deshik Reddy Putluru, Adrian Buganza Tepole, Hector Gomez","doi":"10.1186/s12987-025-00691-4","DOIUrl":"10.1186/s12987-025-00691-4","url":null,"abstract":"<p><p>Cerebrospinal flow dynamics (CSF) plays a critical role in structural disorders of the central nervous system (CNS) and in the design of effective procedures for intrathecal drug delivery. Medical imaging techniques have only partially characterized CSF dynamics. Computational models have the potential to offer a high-resolution description of CSF flow and advance our mechanistic understanding. However, anatomically-accurate computational models of CSF dynamics in the spinal canal have largely ignored the compliance of the spinal tissues, which is critical to understand the pulse wave velocity and the craniocaudal decay of CSF pulsations. Here, we propose a mixed-dimensional fluid-structure interaction method that enables high-fidelity simulations of CSF dynamics on anatomically-accurate models of the spinal canal, considering the tissue compliance effects emerging from the dura mater and epidural fat. Our mixed-dimensional approach bypasses a critical computational bottleneck that emerges from the multiscale geometry of spinal tissues. Our results show that accurate modeling of tissue compliance is critical to capture key elements of CSF dynamics. This work opens new possibilities to control and optimize intrathecal drug delivery and to understand structural abnormalities of the CNS.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"81"},"PeriodicalIF":6.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752829","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":"Identifying a potential role of immune cells in gadolinium deposition within the brain.","authors":"Dixy Parakkattel, Nico Ruprecht, Peter Broekmann, Sarah Guimbal, Chiara Stüdle, Sasha Soldati, Johannes T Heverhagen, Britta Engelhardt, Hendrik von Tengg-Kobligk","doi":"10.1186/s12987-025-00674-5","DOIUrl":"10.1186/s12987-025-00674-5","url":null,"abstract":"<p><strong>Background: </strong>Gadolinium (Gd) deposition in the brain was observed in patients with history of gadolinium-based contrast agent (GBCA) administration. However, the exact mechanism behind this deposition remains unclear, especially given that an intact blood-brain barrier (BBB) is considered impermeable to GBCA. In this study, we propose that immune cells might play a role in facilitating GBCA entry into the brain despite an intact BBB.</p><p><strong>Methods: </strong>Gadoterate meglumine, gadoteridol, gadobutrol and gadodiamide were investigated as GBCAs. Immune cells from human donor buffy coats were isolated, incubated with the GBCA and used in the experiments. Gd associated with the immune cells were measured using single-cell inductively coupled mass spectrometry (SC-ICP-MS). Flow cytometry analysis was performed to characterise the adhesion molecule expression profile on the immune cells and binding assay was employed to check the binding of Gd treated immune cells with endothelial ligands in static conditions. An in vitro model of the human BBB that prevents free diffusion of GBCA across was further used to observe immune cell behaviour at the BBB under physiological flow, in vitro.</p><p><strong>Results: </strong>Our findings confirm that various immune cells, including CD4⁺ T cells, CD8⁺ T cells, monocytes, NK cells and B cells are capable of taking up the different GBCAs. Furthermore, we demonstrate that GBCA loading does not impair immune cell interaction with the endothelial ligands required for successful extravasation across the BBB under static conditions. Most importantly, we show that T cells and monocytes, loaded with the different contrast agents, extravasated across an in vitro BBB model under physiological flow conditions in a comparable manner to non GBCA loaded cells.</p><p><strong>Conclusions: </strong>Taken together, our in vitro observations show that immune cells can transport GBCA across the BBB and could lead to permanent deposition of Gd in the brain.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"80"},"PeriodicalIF":6.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741740","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}