Fluids and Barriers of the CNS最新文献

{"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}

{"title":"Assessing blood-brain barrier (BBB) integrity in an Alzheimer's disease mouse model: is the BBB globally or locally disrupted?","authors":"Ehsan Nozohouri, Behnam Noorani, Dhavalkumar Patel, Yeseul Ahn, Sumaih Zoubi, Ulrich Bickel","doi":"10.1186/s12987-025-00685-2","DOIUrl":"10.1186/s12987-025-00685-2","url":null,"abstract":"<p><p>Alzheimer's disease (AD), marked by amyloid-beta (Aβ) plaques and tau tangles, involves cerebral amyloid angiopathy (CAA), which may compromise blood-brain barrier (BBB) integrity. However, the extent and nature of BBB disruption in AD remain unclear. This study assessed BBB permeability in Tg2576 AD mice by evaluating unidirectional paracellular transport from blood to brain following intravenous injection of the stable isotope-labeled marker [¹³C₁₂]sucrose. Pharmacokinetic analysis of plasma and brain concentrations 30 min post-injection revealed minimal sucrose passage across the BBB in both AD and wild-type (WT) mice, suggesting preserved BBB integrity despite Aβ deposition. Regional clearance rates in the hippocampus, cortex, and cerebellum were similar across groups, with only the olfactory bulbs showing increased uptake. Immunohistochemical analysis of BBB tight junction proteins (claudin-5, occludin, ZO-1) revealed no significant differences between AD and WT mice. High-resolution imaging showed minor tight junction disruptions near Aβ plaques, but laser microdissection and LC-MS/MS analysis revealed no increased sucrose concentrations in regions with vascular Aβ-deposition, indicating localized changes do not substantially affect BBB permeability. Our findings challenge the assumption of widespread BBB leakiness in the Tg2576 AD model, highlighting the need for multi-method approaches to assess BBB integrity and optimize drug delivery in AD.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"79"},"PeriodicalIF":5.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698009","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":"Neisseria meningitidis regulates P-glycoprotein transporter activity in brain endothelial cells via sphingosine 1-phosphate receptor 1.","authors":"Fatemeh Nosratabadi, Leo M Endres, Fabian Schumacher, Heike Claus, Burkhard Kleuser, Brandon J Kim, Alexandra Schubert-Unkmeir","doi":"10.1186/s12987-025-00687-0","DOIUrl":"10.1186/s12987-025-00687-0","url":null,"abstract":"<p><strong>Background: </strong>The brain endothelial cells (BECs) are essential for protecting the central nervous system (CNS) from xenobiotics and pathogens, including Neisseria meningitidis, while maintaining CNS homeostasis through tight junction (TJ) proteins and specialized transporters. Among these, multidrug resistance (MDR) transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are pivotal in restricting the entry of neurotoxic substances. Although the impact of N. meningitidis infection on BBB TJ is well-documented, its effect on MDR transporters remains largely unexplored.</p><p><strong>Methods: </strong>We employed induced pluripotent stem cell-derived brain-like endothelial cells (iBECs) as an in vitro BECs model due to their human-like morphology and expression of junctional proteins and MDR transporters. iBECs were exposed to various N. meningitidis strains, isogenic mutants, heat-inactivated bacteria, conditioned media, or purified capsule polysaccharide (CPS). P-gp and BCRP activities were assessed using intracellular accumulation assays with Rhodamine 123 and Chlorin e6, respectively, in the presence of P-gp inhibitors cyclosporin A and PSC833 and BCRP inhibitor Ko143. Gene expression and protein levels were determined by qPCR and western blotting, and sphingolipid quantification was performed via liquid chromatography tandem-mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>Infection of iBECs with N. meningitidis inhibited P-gp activity, whereas BCRP activity remained unaffected. P-gp inhibition occurred without changes in gene expression or protein abundance. Cells infected with N. meningitidis showed reduced efficacy of P-gp inhibitors, an effect not seen with the BCRP inhibitor Ko143. N. meningitidis CPS was identified as a key factor in modulating P-gp activity. Notably, the inhibitory effect of N. meningitidis on P-gp activity was blocked by a specific sphingosine 1-phosphate receptor 1 (S1PR₁) antagonist as well as by sphingosine kinase inhibitors, revealing a mechanistic link between S1PR₁ signaling and P-gp modulation during infection. Furthermore, S1PR₁ was upregulated in infected iBECs. Although LC-MS/MS measurement showed no increase in S1P levels in infected cells compared to uninfected controls, these findings suggest a crucial role for S1PR₁ signaling in mediating the observed effects.</p><p><strong>Conclusions: </strong>These findings demonstrate that N. meningitidis infection impairs P-gp function through S1PR₁-dependent pathways, suggesting that targeting this signaling cascade may offer a novel therapeutic strategy to preserve BBB integrity during bacterial infections.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"78"},"PeriodicalIF":6.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689698","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":"Neuroprotective role of pyrroloquinoline quinone in folate deficiency-induced blood-brain barrier disruption.","authors":"Sara Aboulhassane, Vishal Sangha, Md Tozammel Hoque, Reina Bendayan","doi":"10.1186/s12987-025-00689-y","DOIUrl":"10.1186/s12987-025-00689-y","url":null,"abstract":"<p><p>Healthy neurodevelopment requires adequate folates (vitamin B9), which are critical for key biosynthetic and homeostatic processes in the central nervous system (CNS). In the brain, folate transport is mediated by three major pathways: folate receptor alpha (FRα), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC). Folate uptake primarily occurs at the blood-cerebrospinal fluid barrier (BCSFB) by concerted actions of FRα and PCFT. Alterations in this transport pathway can result in cerebral folate deficiency (CFD), a rare but devastating pediatric condition associated with neuroinflammation and oxidative stress. Recent findings highlight the blood-brain barrier (BBB) as an alternative route for folate delivery, particularly through RFC upregulation. We hypothesized that pyrroloquinoline quinone (PQQ), an activator of nuclear respiratory factor 1 (NRF-1) and PGC-1α, key regulators of mitochondrial biogenesis, could enhance RFC expression at the BBB and mitigate CFD-induced damage. Using in vitro and in vivo models of folate deficiency, we investigated its impact on BBB integrity, inflammation, oxidative stress, mitochondrial dysfunction, and assessed PQQ's ability to reverse these effects. Human brain microvessel endothelial cells (hCMEC/D3) cultured in control folate-sufficient (FS) or folate-deficient (FD) medium were treated with PQQ (1 or 5 µM) or vehicle control for 24 h. Wildtype (C57BL6/N) mice received FD (0 mg/kg folate), or FS (2 mg/kg folate) diet and underwent a 10-day (20 mg/kg/day, i.p) PQQ treatment. Following treatment, hCMEC/D3 cells and isolated mouse brain capillaries were analyzed using qPCR, ELISA, and immunoblotting to assess gene and protein expression of tight junction proteins, inflammatory and oxidative stress markers, mitochondrial transcription factors, and folate transporters. BBB permeability was evaluated in vivo using the sodium fluorescein (NaFl) assay. FD significantly increased the gene and/or protein expression of inflammatory cytokines/chemokines, endothelial adhesion molecules and oxidative stress markers, while tight junction proteins were significantly downregulated both in vitro and in vivo. The NaFl assay confirmed increased BBB permeability in FD mice. PQQ treatment effectively reversed these changes by upregulating RFC and PCFT expression, restoring BBB permeability, mitigating inflammatory and oxidative stress responses and improving mitochondrial biogenesis via PGC-1α/NRF-1 signaling. These results highlight the impact of brain FD on BBB integrity, potentially contributing to neurological deficits seen in CFD disorders with PQQ providing a promising therapeutic strategy.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"77"},"PeriodicalIF":6.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689699","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":"MRI contrast accumulation in features of cerebral small vessel disease: blood-brain barrier dysfunction or elevated vascular density?","authors":"Tomas Vikner, Anders Garpebring, Cecilia Björnfot, Jan Malm, Anders Eklund, Anders Wåhlin","doi":"10.1186/s12987-025-00675-4","DOIUrl":"10.1186/s12987-025-00675-4","url":null,"abstract":"<p><strong>Background: </strong>White matter lesions (WML) and dilated perivascular spaces (PVS) are features of small vessel disease (SVD), commonly observed in aging and dementia, with unknown pathophysiology. Human studies have documented contrast accumulation within and in proximity of SVD-lesions. However, whether such observations mainly reflect excessive blood-brain barrier (BBB) leakage, or altered microvascular density in the investigated regions, remains unclear.</p><p><strong>Methods: </strong>To evaluate the roles of BBB leakage and vascular density in aging and SVD, dynamic contrast enhanced (DCE) MRI was used to estimate the permeability-surface area product (PS) and fractional plasma volume ([Formula: see text]) in normal-appearing brain tissue and in proximity of and within WML and PVS in a population-based cohort (N = 56; 34/22 m/f; age 64 to 84 years). Analysis of variance (ANOVA) was used to assess regional differences in PS and [Formula: see text] and analysis of covariance (ANCOVA) was used to assess regional differences in PS with [Formula: see text] and vascular risk as covariates.</p><p><strong>Results: </strong>Pronounced increases in PS and [Formula: see text] were observed from normal-appearing white matter (NAWM) to WML peripheries to WMLs. Similar PS and [Formula: see text]increases were observed from basal ganglia (BG) to BG-PVS. Further, PS in NAWM and white matter (WM) PVS were found to increase with cortex-to-ventricular depth. However, ANCOVA models with [Formula: see text] as a covariate showed that variance in PS was mainly explained by v_p (η²=0.17 to η²=0.35; all p < 10^- 3), whereas the effect of region was only borderline-significant when comparing NAWM, WML peripheries and WML (p = 0.03) and non-significant for the other comparisons (p > 0.29).</p><p><strong>Conclusions: </strong>Our findings support the notion that contrast leakage across the BBB accumulates within and in proximity of SVD-related lesions. However, high contrast accumulation may mainly reflect high vascularization, and to a lesser degree than previously recognized BBB dysfunction.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"74"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648969","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":"Apocrine secretion by the choroid plexus.","authors":"Ya'el Courtney, Maria K Lehtinen","doi":"10.1186/s12987-025-00684-3","DOIUrl":"10.1186/s12987-025-00684-3","url":null,"abstract":"<p><p>The choroid plexus (ChP) epithelium secretes cerebrospinal fluid (CSF) and signaling factors that influence brain development. In addition to classical secretory pathways, the ChP also employs apocrine secretion, in which large cytoplasmic portions bud from the apical surface in structures called aposomes. Although historically underappreciated, recent imaging and molecular studies demonstrate that this process is calcium-dependent and regulated by neuromodulators such as serotonin. Apocrine secretion contributes distinct cytoplasmic cargo-proteins, organelles, and signaling molecules-to the CSF, with evidence for developmental roles in neurogenesis and progenitor cell differentiation. This review synthesizes structural, functional, and proteomic data supporting ChP apocrine secretion, compares it to other epithelial release mechanisms, and highlights outstanding questions about its regulation and physiological roles. By focusing on this unconventional and understudied mode of secretion, we provide a framework for understanding how ChP-mediated cargo release shapes the CSF environment and contributes to brain development.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"75"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648967","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":"Imatinib prevents blood-spinal cord barrier disruption by inhibiting PDGFR-mediated JMJD3 expression and activation after spinal cord injury.","authors":"Chan Sol Park, Jee Youn Lee, Tae Young Yune","doi":"10.1186/s12987-025-00690-5","DOIUrl":"10.1186/s12987-025-00690-5","url":null,"abstract":"<p><strong>Background: </strong>After a spinal cord injury (SCI), disruption of the blood-spinal cord barrier (BSCB) leads to secondary injuries, including inflammatory responses and apoptotic cell death, ultimately causing permanent neurological deficits. Imatinib, a tyrosine kinase inhibitor, has been reported to enhance BSCB integrity and improve functional recovery after SCI. However, the mechanism by which imatinib regulates BSCB integrity remains unclear. Recent studies have identified the histone H3K27me3 demethylase JMJD3 as a key mediator of BSCB disruption, with high expression observed in blood vessels after SCI. In this study, we investigated whether imatinib regulates JMJD3 expression and activation through PDGFR signaling, thereby mitigating BSCB disruption following SCI.</p><p><strong>Methods: </strong>Imatinib (100 mg/kg) was administered intraperitoneally to rats subjected to a contusion injury at the T9 level of the spinal cord and was continued daily for 14 days.</p><p><strong>Results: </strong>Our results indicate that imatinib inhibited the phosphorylation of PDGFRα and PDGFRβ, both tyrosine kinase receptors, without affecting their expression levels. Additionally, imatinib reduced JMJD3 and MMP-9 expression and activation in blood vessels, thereby decreasing macrophage infiltration after SCI. In an oxygen-glucose deprivation (OGD)-induced bEnd.3 cell model, phosphorylated PDGFRα and PDGFRβ, along with JMJD3 expression and activation, were significantly upregulated but were effectively inhibited by imatinib treatment. Furthermore, imatinib suppressed secondary damage, including cell death, blood cell infiltration (e.g., neutrophils and macrophages), inflammation, axonal and myelin loss, and lesion volume. These effects collectively resulted in significant improvements in functional recovery after SCI.</p><p><strong>Conclusion: </strong>Based on these findings, we propose that imatinib exerts a neuroprotective effect, in part by inhibiting PDGFR-mediated JMJD3 expression and activation following SCI.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"76"},"PeriodicalIF":5.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648968","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":"Substrate stiffness and shear stress collectively regulate the inflammatory phenotype in cultured human brain microvascular endothelial cells.","authors":"Alexis K Yates, Heather Murray, Andrew Kjar, Daniel Chavarria, Haley Masters, Hyosung Kim, Alexander P Ligocki, Angela L Jefferson, Ethan S Lippmann","doi":"10.1186/s12987-025-00683-4","DOIUrl":"10.1186/s12987-025-00683-4","url":null,"abstract":"<p><p>Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions of these factors towards blood-brain barrier (BBB) impairment and neurovascular dysfunction have not been extensively studied. Here, we developed in vitro models to examine the sensitivity of primary human brain microvascular endothelial cells (BMECs) to substrate stiffness, with or without exposure to fluid shear stress. Using a combination of molecular profiling techniques, we show that BMECs exhibit an inflammatory signature at both the mRNA and protein level when cultured on gelatin substrates of intermediate stiffness (~ 30 kPa) versus soft substrates (~ 6 kPa). Exposure to modest fluid shear stress (1.7 dyne/cm²) partially attenuated this signature, including reductions in levels of soluble chemoattractants and surface ICAM-1. Overall, our results indicate that increased substrate stiffness promotes an inflammatory phenotype in BMECs that is dampened in the presence of fluid shear stress.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"73"},"PeriodicalIF":5.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642193","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":"Restoring brain barriers: an innovative approach for treating neurological disorders.","authors":"Sighild Lemarchant, Britta Engelhardt, Francesca Cicchetti, Gregory J Bix, Annette Janus, Yann Godfrin, Hélène Blasco, Matthew Campbell, Aurélie de Rus Jacquet","doi":"10.1186/s12987-025-00688-z","DOIUrl":"10.1186/s12987-025-00688-z","url":null,"abstract":"<p><p>The complex etiology of neurological disorders is a major challenge to the identification of therapeutic candidates. Tackling brain vascular dysfunction is gaining attention from the scientific community, neurologists and pharmaceutical companies, as a novel disease-modifying strategy. Here, we provide evidence that at least 41% of neurological diseases and related conditions/injuries display a co-pathology of blood-brain and blood-spinal cord barrier alterations and dysfunctions, and we discuss why this figure may represent only a fraction of a larger phenomenon. We further provide clinical evidence that barrier status may contribute to pathological and functional outcomes in patients. Finally, we discuss drug candidates under development to repair brain barriers.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"72"},"PeriodicalIF":5.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607895","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}