Fluids and Barriers of the CNS最新文献

{"title":"Longitudinal changes in ventricular volume after treating aqueduct stenosis through endoscopic third ventriculostomy in adults.","authors":"Florian Ebel, Caterina Mariani, Raphael Guzman, Jehuda Soleman","doi":"10.1186/s12987-025-00654-9","DOIUrl":"https://doi.org/10.1186/s12987-025-00654-9","url":null,"abstract":"<p><strong>Background: </strong>Assessment of ventricular size following endoscopic third ventriculostomy (ETV) often relies on linear measurements and indexes such as the Evans index (EI) and frontal and occipital horn ratio (FOHR). Long-term data on ventricular volume following ETV is scarce, which leads to uncertainties regarding optimal follow-up duration and whether ventricular size correlates with clinical outcomes. This study aims to analyze the longitudinal changes of ventricular volume following ETV for aqueduct stenosis (AS) in adults.</p><p><strong>Methods: </strong>We retrospectively analyzed radiological images and clinical records of adult patients who underwent ETV for AS between the years 2010 and 2020. The primary endpoint was the change in lateral and third ventricular (LTV) volume at various follow-up periods in patients who did not require revision surgery (successful ETV group). Cluster analysis was performed to identify distinct volumetric patterns, and logistic regression was used to analyze the correlation between ventricular volume changes and clinical symptom improvement.</p><p><strong>Results: </strong>A total of 238 radiological images with 197 (82.8%) MRI and 41 (17.2%) CT scans from 46 patients were analyzed. Thirty-nine (84.8%) patients did not require revision surgery (successful ETV group). In the successful ETV group, LTV volume decreased by 19.6% within 3 months, 31% after 3-6 months, and 47.5% after 6-12 months. Two main clusters were identified: one with a mean LTV volume decrease of 56% and the other of 18.9% after 1 year. The presence of a pineal or tectal lesion (OR 3.94, p = 0.074) tended to be predictive of the former cluster, and the presence of a membrane in the aqueduct (OR 5.1, p = 0.036) was predictive of the latter. Volumetric changes were significantly greater than those measured by EI and FOHR postoperatively (p < 0.001) and at the last follow-up (p = 0.002). There was no association between LTV volume reduction and clinical improvement during the follow-up period (OR 1.03, [95% CI 0.99-1.06]; p = 0.195).</p><p><strong>Conclusion: </strong>Volumetric analysis provides a more accurate representation of ventricular size changes following ETV for AS. It demonstrates a continuous reduction in LTV volume during the first year after surgery, whereafter LTV volume appears to stabilize with a cumulative reduction of 38.7%, suggesting that lifelong imaging may be unnecessary in these patients. However, it does not predict the clinical outcome.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"42"},"PeriodicalIF":5.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965098","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":"Glucagon-like peptide-1 receptor modulates cerebrospinal fluid secretion and intracranial pressure in rats.","authors":"Mette N Jensen, Ida M E Israelsen, Jonathan H Wardman, Dennis B Jensen, Daniel B Andersen, Trine L Toft-Bertelsen, Martin F Rath, Jens Juul Holst, Mette M Rosenkilde, Nanna MacAulay","doi":"10.1186/s12987-025-00652-x","DOIUrl":"https://doi.org/10.1186/s12987-025-00652-x","url":null,"abstract":"<p><strong>Background: </strong>Cerebrospinal fluid (CSF) is produced and absorbed at a balanced rate to maintain a constant intracranial pressure (ICP). The CSF dynamics are, however, disturbed in several pathological conditions, leading to elevated ICP, which may have fatal outcomes if left untreated. Treatment options for these conditions are limited to invasive neurosurgery, and novel pharmacological approaches to manage ICP in pathology are sought. Here, we aimed to demonstrate the potential of the glucagon-like peptide-1 receptor (GLP-1R) as such a target.</p><p><strong>Methods: </strong>We administered male rats with intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) GLP-1R agonist (exendin-4) or antagonist (exendin-9-39) followed by in vivo determination of CSF dynamics. GLP-1R expression in the CSF-secreting choroid plexus was demonstrated with RNAScope in situ hybridization and western blotting and transporter activity with radio-isotope flux assays.</p><p><strong>Results: </strong>GLP-1R activation increased the CSF secretion rate with an associated elevation of the ICP, whereas inhibition of the receptor reduced the rate of CSF secretion. These effects were observed with central, but not peripheral, administration of the agonist and antagonist, suggesting receptor expression on the luminal, CSF-facing side of the choroid plexus, which aligned with GLP-1R-mediated modulation of luminally-expressed transporters in excised choroid plexus. Low level GLP-1R expression was demonstrated in the choroid plexus at mRNA and protein levels.</p><p><strong>Conclusion: </strong>Modulation of GLP-1R affects CSF production, which suggests that GLP-1R-mediated signalling may have the potential to control ICP in pathological conditions with disturbed CSF homeostasis.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"41"},"PeriodicalIF":5.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960772","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":"Correction: The utility of customised tissue probability maps and templates for patients with idiopathic normal pressure hydrocephalus: a computational anatomy toolbox (CAT12) study.","authors":"Shigenori Kanno, Junyan Liu, Ai Kawamura, Shoko Ota, Nobuko Kawakami, Chifumi Iseki, Kazuo Kakinuma, Shiho Matsubara, Kazuto Katsuse, Kazushi Sato, Takashi Takeuchi, Yoshitaka Tanaka, Hiroyasu Kodama, Tatsuo Nagasaka, Masahiro Sai, Hayato Odagiri, Mioko Saito, Kentaro Takanami, Shunji Mugikura, Kyoko Suzuki","doi":"10.1186/s12987-025-00655-8","DOIUrl":"https://doi.org/10.1186/s12987-025-00655-8","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"40"},"PeriodicalIF":5.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971521","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":"The role of the RING finger protein 213 gene in Moyamoya disease.","authors":"Xinpeng Deng, Shaosen Zhang, Runsheng Zhao, Wei Liu, Weihong Huang, Xuanlin Chen, Xiang Gao, Yi Huang, Dong Zhang","doi":"10.1186/s12987-025-00649-6","DOIUrl":"https://doi.org/10.1186/s12987-025-00649-6","url":null,"abstract":"<p><p>Moyamoya Disease (MMD) represents a chronic and progressive cerebrovascular disorder characterized by the gradual occlusion of the terminal portions of the bilateral internal carotid arteries and their major branches, accompanied by the formation of abnormal vascular networks at the base of the skull. In adolescents, particularly in pediatric populations, MMD is a significant cause of stroke, posing a severe challenge to human health and imposing a heavy burden on healthcare systems. Ring Finger Protein 213 (RNF213), as the primary susceptibility gene for MMD, plays a crucial regulatory role in the initiation, progression, and prognosis of the disease. Despite extensive research on the role of RNF213 in the pathogenesis of MMD, the underlying molecular mechanisms remain incompletely understood and represent a pressing scientific challenge requiring further exploration. This review aims to synthesize the latest research findings and systematically elucidate the multifaceted roles of RNF213 in MMD, including genetic susceptibility, immune-inflammatory responses, blood-brain barrier(BBB) disruption, and angiogenesis. By integrating these findings, this study seeks to provide new insights and theoretical support for a comprehensive and in-depth understanding of the pathophysiological processes of MMD. This research not only contributes to further unraveling the complex pathogenesis of MMD but also lays a solid theoretical foundation for the development of targeted preventive and therapeutic strategies.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"39"},"PeriodicalIF":5.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958732","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":"Reactive astrocyte-derived exosomes enhance intracranial lymphatic drainage in mice after intracranial hemorrhage.","authors":"Kexin Li, Yuheng Liu, Junjie Gong, Jing Li, Mingyu Zhao, Chengyou Hong, Yuchi Zhang, Mengyao He, Zhenye Zhu, Zhijuan Chen, Zengguang Wang","doi":"10.1186/s12987-025-00651-y","DOIUrl":"https://doi.org/10.1186/s12987-025-00651-y","url":null,"abstract":"<p><strong>Background: </strong>After intracranial hemorrhage (ICH), the formation of primary hematoma foci leads to the development of secondary brain injury factors such as perihematomal edema (PHE) and accumulation of toxic metabolites, which severely affect the survival and prognosis of patients. The intracerebral lymphatic system, proposed by Jeffrey J. Iliff et al., plays an important role in central nervous system (CNS) fluid homeostasis and waste removal, while reactive astrocyte-derived exosomes have shown therapeutic potential in CNS disorders. Our study focuses on the effects of hemin-treated reactive astrocyte-derived exosomes on the functional integrity of the glymphatic system (GLS) after ICH and their potential mechanism of action in repairing brain injury.</p><p><strong>Methods: </strong>Hemin, an iron-rich porphyrin compound, was used to construct the in vitro model of ICH. Primary astrocytes were treated with complete medium supplemented with different concentrations of hemin to obtain exosomes secreted by them, and mice with ICH induced by the collagenase method were intervened by intranasal administration. Solute clearance efficiency was assessed by intracranial injection of cerebrospinal fluid tracers and fluorescent magnetic beads. Immunofluorescence analysis of Aquaporin 4 (AQP4) polarization and astrocyte proliferation. Magnetic Resonance Imaging was used to visualize and quantify the volume of hematoma foci and PHE, and Western Blot was used to analyze the accumulation of toxic metabolites, while neuronal apoptosis was detected by a combination of TUNEL assay apoptosis detection kit and Nissl staining, and their functional status was analyzed. Gait analysis software was used to detect functional recovery of the affected limb in mice.</p><p><strong>Results: </strong>Exosomes from hemin treated astrocytes facilitated the recovery of AQP4 polarization and attenuated astrocyte proliferation around hematoma foci in mice with ICH, thereby promoting the recovery of the GLS. Meanwhile, exosomes from hemin treated astrocytes reduced PHE and toxic protein accumulation, decreased apoptosis of cortical neurons on the affected side, and facilitated recovery of motor function of the affected limb, and these effects were blocked by TGN020, an AQP4-specific inhibitor.</p><p><strong>Conclusions: </strong>Exosomes from hemin treated astrocytes attenuated secondary brain injury and neurological deficits in mice with ICH by promoting the repair of GLS injury.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"37"},"PeriodicalIF":5.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005654","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":"Erythrocyte-derived extracellular vesicles transcytose across the blood-brain barrier to induce Parkinson's disease-like neurodegeneration.","authors":"Hélèna L Denis, Aurélie de Rus Jacquet, Melanie Alpaugh, Michel Panisset, Roger A Barker, Éric Boilard, Francesca Cicchetti","doi":"10.1186/s12987-025-00646-9","DOIUrl":"https://doi.org/10.1186/s12987-025-00646-9","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative illness characterized by motor and non-motor features. Hallmarks of the disease include an extensive loss of dopaminergic neurons in the substantia nigra pars compacta, evidence of neuroinflammation, and the accumulation of misfolded proteins leading to the formation of Lewy bodies. While PD etiology is complex and identifying a single disease trigger has been a challenge, accumulating evidence indicates that non-neuronal and peripheral factors may likely contribute to disease onset and progression. The brain is shielded from peripheral factors by the blood-brain barrier (BBB), which tightly controls the entry of systemic molecules and cells from the blood to the brain. The BBB integrates molecular signals originating from the luminal (blood) and abluminal (brain) sides of the endothelial wall, regulating these exchanges. Of particular interest are erythrocytes, which are not only the most abundant cell type in the blood, but they also secrete extracellular vesicles (EVs) that display disease-specific signatures over the course of PD. Erythrocyte-derived EVs (EEVs) could provide a route by which pathological molecular signals travel from the periphery to the central nervous system. The primary objective of this study was to evaluate, in a human-based platform, mechanisms of EEV transport from the blood to the brain under physiological conditions. The secondary objective was to determine the ability of EEVs, generated by erythrocytes of healthy donors or patients, to induce PD-like features. We leveraged two in vitro models of the BBB, the transwell chambers and a microfluidic BBB chip generated using human induced pluripotent stem cells. Our findings suggest that EEVs transcytose from the vascular to the brain compartment of the human BBB model via a caveolin-dependant mechanism. Furthermore, EEVs derived from individuals with PD altered BBB integrity compared to healthy EEV controls, and clinical severity aggravated the loss of barrier integrity and increased EEV extravasation into the brain compartment. PD-derived EEVs reduced ZO-1 and Claudin 5 tight junction levels in BMEC-like cells and induced the selective atrophy of dopaminergic neurons. In contrast, non-dopaminergic neurons were not affected by treatment with PD EEVs. In summary, our data suggest that EEV interactions at the human BBB can be studied using a highly translational human-based brain chip model, and EEV toxicity at the neurovascular unit is exacerbated by disease severity.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"38"},"PeriodicalIF":5.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981732","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":"The effects of dose, valency, and affinity on TfR-mediated brain delivery in vivo.","authors":"Gillian Bonvicini, Sunitha Singh, Lisa Sandersjöö, Dag Sehlin, Stina Syvänen, Ken G Andersson","doi":"10.1186/s12987-025-00643-y","DOIUrl":"10.1186/s12987-025-00643-y","url":null,"abstract":"<p><strong>Background: </strong>Monovalent binding to the transferrin receptor (TfR) is considered the most efficient mode for high delivery of protein constructs across the blood-brain barrier via TfR-mediated transcytosis at therapeutic doses. However, growing evidence suggests this is not the case at lower, diagnostic doses. There is also a lack of data on how valency and affinity to TfR affect brain uptake independently since previous studies have not compared monovalent and bivalent antibodies with similar affinities regardless of valency (i.e. apparent affinity). Therefore, the aim was to evaluate the independent effects of valency and affinity on TfR-mediated brain delivery at different doses.</p><p><strong>Methods: </strong>Affinity variants of antibody 8D3 were produced by introducing alanine point mutations into the complementarity-determining regions. Eleven Fab fragments and 29 IgGs were affinity screened against mouse TfR (mTfR). Six of each were chosen for production with a knob-into-hole design to have monovalent and bivalent TfR binders in full-length antibody format. The apparent affinity of these 12 antibodies were tested in an Sp2/0-Ag14 cell assay. The 10 nM apparent affinity set and the bivalent wild-type antibody were radiolabelled and injected into wild-type mice at a low (0.22 ± 0.03 mg/kg) or high (7.5 ± 0.43 mg/kg) dose. The biodistribution was measured in brain, blood and peripheral organs 4 h post-injection.</p><p><strong>Results: </strong>Two sets of monovalent and bivalent 8D3 formats with similar mTfR apparent affinities were identified. Brain and tissue uptake was higher at the low dose than the high dose for all antibodies. At the low dose, the higher apparent affinity, bivalent antibody had higher brain uptake than either of the two lower apparent affinity antibodies. At the high dose, the monovalent antibody had higher brain uptake than the two bivalent antibodies. The peripheral distribution of the three antibodies were similar to the brain distribution at both doses.</p><p><strong>Conclusions: </strong>Valency and apparent affinity affect brain uptake in a dose-dependent manner such that: brain uptake was affected more by apparent affinity at the low dose and by valency at the high dose. Thus, when designing constructs for TfR-mediated brain delivery, the application, and consequently the dose, are critical to consider.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"36"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810790","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":"Hyphal penetration is the major pathway of translocation of Candida albicans across the blood-cerebrospinal fluid barrier.","authors":"S Schmidt, C Schwerk, H Schroten, H Ishikawa, R Schubert, T Lehrnbecher, H Rudolph","doi":"10.1186/s12987-025-00644-x","DOIUrl":"10.1186/s12987-025-00644-x","url":null,"abstract":"<p><strong>Background: </strong>Despite the availability of potent antifungal compounds, invasive fungal disease poses significant morbidity and mortality in immunocompromised patients. Candida albicans is one of the leading pathogens in this setting, and may affect the central nervous system (CNS), which is an extremely severe form of the infection. As the exact pathogenesis of Candida CNS infection is not clear, we investigated the mechanisms and effects of C. albicans transmigration into the CNS, which will be helpful for diagnosis, prevention and treatment.</p><p><strong>Methods: </strong>We used a human in vitro model of the Blood-Cerebrospinal Fluid Barrier (BCSFB), and we investigated the mechanisms of Candida albicans translocation into the CNS. Translocation was evaluated using immunofluorescence analysis focusing on tight and adherens junctions and the actin cytoskeleton. Barrier integrity was monitored via measurement of transepithelial resistance and the paracellular permeability of dextran. LIVE/DEAD assays were applied for viability controls and a cytometric bead array was performed to detect cytokine secretion of plexus epithelial cells.</p><p><strong>Results: </strong>Translocation at low doses occurs transcellularly in the absence of cytotoxicity or secretion of proinflammatory cytokines. This is accomplished by the formation of a tunnel-like structure exploiting the actin cytoskeleton. With higher infection doses of Candida albicans, a reduction in barrier integrity due to disruption of tight and adherens junctions was observed and cytotoxicity also increased.</p><p><strong>Conclusion: </strong>Our findings reveal that Candida albicans can use transcellular translocation to invade into the CNS and is able to circumvent major host immune response, which may impact on diagnostic and preventive strategies.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"34"},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779575","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":"Enlarged choroid plexus is linked with poorer physical function in rural older adults: a population-based study.","authors":"Qianqian Xie, Ziwei Chen, Jiafeng Wang, Huisi Zhang, Yan Wang, Xiaoyu Wang, Chunyan Li, Yongxiang Wang, Lin Cong, Daniel Ferreira, Anna-Karin Welmer, Lin Song, Yifeng Du, Chengxuan Qiu","doi":"10.1186/s12987-025-00642-z","DOIUrl":"10.1186/s12987-025-00642-z","url":null,"abstract":"<p><strong>Background: </strong>The choroid plexus (ChP) plays an important role in producing cerebrospinal fluid (CSF) and physical dysfunction has been associated with alterations in CSF circulation. However, no population-based studies have thus far examined the association of ChP with physical function in older people.</p><p><strong>Methods: </strong>This population-based cross-sectional study included 1217 participants (age ≥ 60 years; 57.35% women) in the MRI substudy of the Multimodal Interventions to delay Dementia and disability in rural China. ChP volume was automatically segmented using three-dimensional T1-weighted sequences. Physical function was assessed using the Short Physical Performance Battery (SPPB). Data were analyzed using general linear regression and mediation models.</p><p><strong>Results: </strong>Controlling for demographic characteristics, cardiovascular risk factors, stroke, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and total intracranial volume, per 1-ml increase in ChP volume was associated with β-coefficient of -0.24 (95% confidence interval: -0.37 to -0.11) for SPPB summary score, with the association being stronger in females (-0.40; -0.60 to -0.20) than in males (-0.17; -0.33 to -0.01) (p for ChP volume×sex interaction = 0.028). The associations were similar across three domains of balance, chair stand, and walking speed. In addition, enlarged ChP volume was associated with increased ventricular volume and white matter hyperintensity (WMH) volume. Mediation analysis suggested that lateral ventricular volume and periventricular WMH volume significantly mediated the association of ChP volume with the SPPB summary score, with the proportion of mediation being 54.22% and 14.48%, respectively.</p><p><strong>Conclusion: </strong>Larger ChP volume is associated with poorer physical function in older adults, especially in women. The association is largely mediated by lateral ventricular and periventricular WMH volumes.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"33"},"PeriodicalIF":5.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771841","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":"Rutin ameliorates stress-induced blood‒brain barrier dysfunction and cognitive decline via the endothelial HDAC1‒Claudin-5 axis.","authors":"Zhao-Wei Sun, Zhao-Xin Sun, Yun Zhao, Ling Zhang, Fang Xie, Xue Wang, Jin-Shan Li, Mao-Yang Zhou, Hong Feng, Ling-Jia Qian","doi":"10.1186/s12987-025-00639-8","DOIUrl":"10.1186/s12987-025-00639-8","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that chronic stress compromises blood‒brain barrier (BBB) integrity by disrupting brain microvascular endothelial cells (BMECs), contributing to the development of cognitive impairments. Thus, targeting the BBB is expected to be a promising treatment strategy. The biological function of rutin has been investigated in neurological disorders; however, its regulatory role in stress-induced BBB damage and cognitive decline and the underlying mechanisms remain elusive.</p><p><strong>Methods: </strong>In a chronic unpredictable mild stress (CUMS) mouse model, a fluorescent dye assay and behavioral tests, including a novel object recognition test and Morris water maze, were performed to evaluate the protective effects of rutin on BBB integrity and cognition. The effects of rutin on BMEC function were also investigated in hCMEC/D3 cells (a human brain microvascular endothelial cell line) in vitro. Furthermore, the molecular mechanisms by which rutin restores BBB endothelium dysfunction were explored via RNA-seq, quantitative real-time PCR, western blotting, immunofluorescence and chromatin immunoprecipitation. Finally, biotinylated tumor necrosis factor-α (TNF-α) was employed to test the influence of rutin on the ability of circulating TNF-α to cross the BBB.</p><p><strong>Results: </strong>We identified that rutin attenuated BBB hyperpermeability and cognitive impairment caused by the 8-week CUMS procedure. Moreover, rutin promoted the proliferation, migration and angiogenesis ability of BMECs, and the integrity of the cellular monolayer through positively regulating the expression of genes involved. Furthermore, rutin impeded histone deacetylase 1 (HDAC1) recruitment and stabilized H3K27ac to increase Claudin-5 protein levels. Ultimately, normalization of the hippocampal HDAC1‒Claudin-5 axis by rutin blocked the infiltration of circulating TNF-α into the brain parenchyma and alleviated neuroinflammation.</p><p><strong>Conclusions: </strong>This work establishes a protective role of rutin in regulating BMEC function and BBB integrity, and reveals that rutin is a potential drug candidate for curing chronic stress-induced cognitive deficits.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"35"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771854","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}