Yang Yang, Dandan Guo, Qingchao Yang, Chenlu Yang, Jinde Liu, Heyin Liu, Wen Liu, Yuqian Liu, Yi Li, Yiming Liu
{"title":"Peripheral inflammatory state in idiopathic normal pressure hydrocephalus patients: a cross-sectional study.","authors":"Yang Yang, Dandan Guo, Qingchao Yang, Chenlu Yang, Jinde Liu, Heyin Liu, Wen Liu, Yuqian Liu, Yi Li, Yiming Liu","doi":"10.1186/s12987-025-00682-5","DOIUrl":"10.1186/s12987-025-00682-5","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation may be involved in the pathogenesis of idiopathic normal pressure hydrocephalus (iNPH). However, the specific changes in the peripheral inflammatory state of patients with iNPH remain unclear.</p><p><strong>Objective: </strong>To explore the changes in the peripheral inflammatory state of patients with iNPH and their potential value as biomarkers of clinical diagnosis and disease severity.</p><p><strong>Methods: </strong>In this cross-sectional study, 119 iNPH patients with AD-negative pathology and 200 healthy controls (HCs) were enrolled. Clinical characteristics, including the Idiopathic Normal Pressure Hydrocephalus Grading Scale (iNPHGS), Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), were collected along with inflammatory parameters in the peripheral blood. Logistic regression was applied to evaluate differences in peripheral inflammatory indicators, adjusting for age, sex, and comorbidities. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of the inflammatory markers. Correlations between inflammatory parameters and clinical characteristics were assessed.</p><p><strong>Results: </strong>Significant differences in inflammatory parameters, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and prognostic nutritional index (PNI), were observed between iNPH patients and HCs after adjusting for age, sex and comorbidities. The combination of PNI and platelet-to-high-density lipoprotein ratio (PHR) distinguished iNPH patients from HCs most significantly (area under the curve [AUC] = 0.820). Neutrophil ratio and lymphocyte ratio were associated with clinical severity and cognitive impairment of patients with iNPH.</p><p><strong>Conclusions: </strong>iNPH patients exhibit an elevated peripheral inflammatory state. Peripheral inflammatory parameters, especially neutrophil ratio and lymphocyte ratio, are associated with disease severity and cognitive impairment, suggesting their potential as therapeutic targets and offering new insights into the pathophysiology of iNPH. Additionally, the inflammatory peripheral parameters may serve as valuable and convenient method in assisting clinical diagnosis.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"71"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590799","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}
Ana Špilak, Adrián Klepe, Sophia Theresa Kriwanek, Heinz-Peter Friedl, Andreas Brachner, Christa Nöhammer, Winfried Neuhaus
{"title":"Uptake of DU145 and LNCaP prostate cancer cell line derived extracellular vesicles is inversely correlated with blood-brain barrier integrity in vitro.","authors":"Ana Špilak, Adrián Klepe, Sophia Theresa Kriwanek, Heinz-Peter Friedl, Andreas Brachner, Christa Nöhammer, Winfried Neuhaus","doi":"10.1186/s12987-025-00680-7","DOIUrl":"10.1186/s12987-025-00680-7","url":null,"abstract":"<p><strong>Background: </strong>Tumor-derived small extracellular vesicles (sEVs) have been implicated in changes of the blood-brain barrier (BBB) during pre-metastatic niche formation. Although it was postulated that sEVs can traverse the highly restrictive BBB via transcytosis-data mostly based on the indirect detection of transported cargo-direct evidence for sEV transport across the BBB remains elusive due to challenges in sEV labelling, detection limits, and inherent limitations of existing in vitro BBB models. This study investigated the interaction and effects of sEVs derived from low (LNCaP) and moderately metastatic (DU145) prostate cancer (PCa) cell lines with the human brain endothelial cell line hCMEC/D3.</p><p><strong>Methods: </strong>Systematic optimization of the cell culture membrane insert set-up for sEV transport studies was accomplished with inserts with different pore sizes, varied coating procedures and medium compositions. Particle size distribution, quantification and zeta-potential was measured with nanoparticle tracking analysis. Uptake of fluorescent labelled sEVs by hCMEC/D3 cell layers was determined by flow cytometry, barrier integrity was measured by transendothelial electrical resistance (TEER). Effects of inflammatory cytokines and PCa lines-derived sEVs on hCMEC/D3 at the transcriptomic level were investigated by means of high-throughput qPCR based on Fluidigm Biomark® platform.</p><p><strong>Results: </strong>Improved conditions for sEV transport studies included the application of membrane inserts with 1 µm pore size and of 1% BSA in the receiver compartment. Efficiency of LNCaP- and DU145-derived sEV uptake by hCMEC/D3 cells revealed an inverse correlation between uptake of sEVs and paracellular barrier integrity (TEER). Whereas addition of sEVs of the more aggressive DU145 cells resulted in a distinct increase of TEER under regular and inflammatory conditions, LNCaP-derived sEVs affected TEER only upon inflammatory cytokine treatment. MRNA expression analyses of hCMEC/D3 cells revealed a distinct regulation of transcripts depending on TEER (i.a. FN, CDLN1) or upon inflammatory cytokines (i.a.: ABCB1, MFSD2a, VCAM1, VEGFa).</p><p><strong>Conclusions: </strong>Differences upon treatment of hCMEC/D3 layers with LNCaP-and DU145 derived sEVs indicated that vesicles retain and transport molecular features of their originating cells. Careful optimization of the test set-up for studies with sEVs in vitro is recommended, including medium controls for sEV purification and labelling as well as addition of proteins for sEV recovery.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"70"},"PeriodicalIF":5.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583506","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":"Characteristics of patients with idiopathic normal pressure hydrocephalus for whom neurosurgeons hesitate to perform shunt surgery: a nationwide hospital-based survey in Japan.","authors":"Ryo Kawai, Hiroaki Kazui, Tetsuya Ueba, Natsuko Nakamura, Marina Minami, Madoka Nakajima, Shigeki Yamada, Haruhiko Kishima, Hideki Kanemoto, Chifumi Iseki, Etsuro Mori","doi":"10.1186/s12987-025-00681-6","DOIUrl":"10.1186/s12987-025-00681-6","url":null,"abstract":"<p><strong>Background: </strong>There is no consensus regarding the indications for shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH) aged ≥ 85 years or in those with severe physical or mental comorbidities. This nationwide study investigates the current approaches of neurosurgeons regarding iNPH treatment and surgical indications.</p><p><strong>Methods: </strong>A questionnaire, developed in collaboration with neurosurgeons and dementia specialists, was distributed to 1,220 facilities from October 10, 2023. Responses were collected through December 11, 2023 and analyzed to assess current practices and factors influencing surgical decisions.</p><p><strong>Results: </strong>In total, 656 facilities (53.8%) responded. Of them, 30 (4.6%) had a policy of not performing shunt surgery at their own facility and referred patients to other appropriate facilities, and 139 (21.2%) did not perform any shunt surgeries in 2022. The most common number of shunt surgeries performed in 2022 was 1-5 surgeries per facility, accounting for 257 facilities (57.1%). Regarding age-related indications for shunt surgery, 159 facilities (35.3%) reported no age restrictions, whereas 155 facilities (57.8%) among the 268 facilities considering age (59.6%) responded that patients aged ≥ 90 years were not indicated for shunt surgery. Among 450 facilities that performed shunt surgeries in 2022, hesitations resulting from comorbidities were reported as follows: cerebrovascular disease (10.0%), orthopedic disease (11.5%), dialysis (29.8%), Parkinson's syndrome (19.5%), Alzheimer's disease (AD) (42.7%), schizophrenia (44.2%), absence of disproportionately enlarged subarachnoid space hydrocephalus (DESH) (41.5%), and insufficient care or institutionalization (56.0%). Logistic regression analyses showed that the number of shunt surgeries performed in 2022 was significant predictor of age ≥ 90 years, cerebrovascular disease, Parkinson's syndrome, AD, no DESH, and insufficient care or institutionalization. Significant predictors for dialysis, AD, and schizophrenia included the presence of collaborating internal medicine facilities. For dialysis and AD, the classification of facilities and having a qualified dementia specialist were significant predictors, respectively.</p><p><strong>Conclusions: </strong>A number of Japanese neurosurgeons hesitate to perform shunt surgery in patients with iNPH aged ≥ 90 years, with comorbid AD or schizophrenia, lacking DESH findings, or having insufficient care support or are institutionalized. Multidisciplinary collaboration with internal medicine, including neurology and psychiatry, may help expand appropriate surgical indications for these patients.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"69"},"PeriodicalIF":5.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564728","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}
Miriam Zamorano, Sanjna Udtha, Aidan M Collier, Erica Underwood, Razan El Sayed, Ankit Agarwal, Devin S Hatchell, Chunfeng Tan, Paul J Nietert, Scott D Olson, Brandon A Miller
{"title":"Transcriptomic and histological characteristics of innate immune activation in brain parenchyma in a rat model of neonatal intraventricular hemorrhage.","authors":"Miriam Zamorano, Sanjna Udtha, Aidan M Collier, Erica Underwood, Razan El Sayed, Ankit Agarwal, Devin S Hatchell, Chunfeng Tan, Paul J Nietert, Scott D Olson, Brandon A Miller","doi":"10.1186/s12987-025-00678-1","DOIUrl":"10.1186/s12987-025-00678-1","url":null,"abstract":"<p><strong>Background: </strong>Intraventricular hemorrhage (IVH) remains a major complication in preterm infants with lifelong sequelae. There is no effective treatment for IVH other than supportive care and surgery for post-hemorrhagic hydrocephalus. We previously reported that the innate neuroimmune response in an animal model of IVH was dependent on developmental stage, only occurring in older animals.</p><p><strong>Methods: </strong>This study utilized a lysed-blood injection model of IVH in rats. This model specifically captures the effects of blood products released by IVH on brain parenchyma. We performed RNAseq and differential gene expression analysis on CD11b/c-positive cells in the brain (microglia/macrophages) to define gene expression in innate immune cells after IVH. We examined CD68 expression, a marker of activated microglia/infiltrating macrophages, in the periventricular white matter after IVH over 90 days. Using IBA1 staining with skeletonized branch analysis and secondary individual cell Sholl analysis, we characterized morphological changes in innate immune cells after IVH. Glial fibrillary protein (GFAP) staining was used to assess astrogliosis and chronic glial scar formation after IVH. We also examined CD68 expression in brain samples from human infants with or without IVH.</p><p><strong>Results: </strong>RNAseq of isolated innate immune cells showed significant differences in cytokine-mediated gene expression at 24 h in IVH versus control animals. CD68 expression in white matter decreased overall with time and was elevated at 7 days in the IVH group compared to controls. IBA1 labeling, when analyzed across all time points, showed significant changes to microglial/macrophage branch number, branch area, and soma area after IVH. Sholl analysis of individual IBA1 labeled cells showed an effect of time but not IVH on microglial/macrophage morphology. At the chronic timepoint of 90 days, IVH induced astrogliosis at the margin of the lateral ventricle. A brain sample from a human infant with IVH showed increased CD68 expression throughout the occipital cortex compared with a non-IVH control, indicating immune activation in brain parenchyma after IVH.</p><p><strong>Conclusions: </strong>Intraventricular blood products induce a robust innate immune response shortly after injection. RNAseq and CD68 counts are more sensitive to differences between groups than morphological immune cell analysis. Gliosis at the edge of ependyma occurs over time. These results help establish the timeline of inflammation after IVH to better define the window for treating IVH-associated inflammation and subsequent brain injury.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"68"},"PeriodicalIF":5.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559615","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}
F J Parras-Martos, A L Sánchez, C Martínez-Bazán, W Coenen, C Gutiérrez-Montes
{"title":"On reduced-order modeling of drug dispersion in the spinal canal.","authors":"F J Parras-Martos, A L Sánchez, C Martínez-Bazán, W Coenen, C Gutiérrez-Montes","doi":"10.1186/s12987-025-00657-6","DOIUrl":"10.1186/s12987-025-00657-6","url":null,"abstract":"<p><p>The optimization of intrathecal drug delivery procedures requires a deeper understanding of flow and transport in the spinal canal. Numerical modeling of drug dispersion is challenging due to the disparity in time scales: dispersion occurs over 1 hour, while cerebrospinal fluid pulsations driven by cardiac motion occur on a 1-second scale. Patient-specific predictions in clinical settings demand simplified descriptions that focus on drug-dispersion times, bypassing the rapid concentration oscillations caused by cyclic motion. A previously derived reduced-order model involving convective transport driven by mean Lagrangian drift is tested here through comparisons with MRI-informed direct numerical simulations (DNS) of drug dispersion in a cervical-canal model featuring nerve rootlets and denticulate ligaments. The comparisons demonstrate that the reduced model is able to describe precisely drug transport, enabling drug-dispersion predictions at a fraction of the computational cost involved in the DNS. Approximate descriptions assuming convective transport to be governed by the mean Eulerian velocity are found to significantly underpredict drug dispersion, highlighting the critical role of mean Lagrangian motion. Our results also confirm the substantial influence of microanatomical features on drug dispersion, consistent with earlier analyses. A key additional finding from the DNS is that molecular diffusion has a negligible impact on drug dispersion, with the mean drift of fluid particles primarily dictating the evolution of the drug distribution-an insight valuable for future modeling efforts.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"66"},"PeriodicalIF":5.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539671","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}
Per Kristian Eide, Markus Hovd, Are Pripp, Øivind Gjertsen, Grethe Løvland, Aslan Lashkarivand, Erika Lindstrøm, Lars Magnus Valnes, Geir Ringstad
{"title":"Altered brain fluid dynamics in spontaneous intracranial hypotension.","authors":"Per Kristian Eide, Markus Hovd, Are Pripp, Øivind Gjertsen, Grethe Løvland, Aslan Lashkarivand, Erika Lindstrøm, Lars Magnus Valnes, Geir Ringstad","doi":"10.1186/s12987-025-00679-0","DOIUrl":"10.1186/s12987-025-00679-0","url":null,"abstract":"<p><strong>Background: </strong>This prospective observational study explored alterations in brain fluid dynamics in patients with spontaneous intracranial hypotension (SIH) and confirmed spinal cerebrospinal fluid (CSF) leakage, specifically addressing CSF clearance to blood, glymphatic influx and measures of CSF flow.</p><p><strong>Methods: </strong>A cohort of SIH patients with verified spinal CSF leaks was compared with an age- and sex-matched reference group having no CSF disturbance or neurological disorders. Prior to repair of CSF leakage, CSF clearance was quantified using population pharmacokinetics, glymphatic influx was assessed by intrathecal contrast-enhanced magnetic resonance imaging (MRI), and CSF flow patterns were measured using either phase-contrast MRI or multi-phase analysis of CSF tracer transport within the subarachnoid spaces.</p><p><strong>Results: </strong>The study included eight SIH cases and nine reference subjects. SIH was accompanied with a greater CSF clearance, severely reduced tracer enrichment in the subarachnoid spaces and impaired glymphatic influx throughout the brain, after the patients had been upright. However, with patients in the supine position during MRI scanning, times to first enrichment of tracer in cisterna magna or perivascular subarachnoid spaces were not affected, with no changes in CSF flow through the Sylvian aqueduct, indicating that ventricular CSF production remained unaffected.</p><p><strong>Conclusions: </strong>SIH caused by spinal CSF leakage is accompanied with altered brain fluid dynamics, here illustrated by accelerated CSF clearance to blood and reduced glymphatic influx, likely due to reduced CSF volume load to the intracranial compartment in the upright position.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"65"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539669","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}
Mina Martine Frey, Negar Zohoorian, Nadia Skauli, Ole Petter Ottersen, Mahmood Amiry-Moghaddam
{"title":"Are diurnal variations in glymphatic clearance driven by circadian regulation of Aquaporin-4 expression?","authors":"Mina Martine Frey, Negar Zohoorian, Nadia Skauli, Ole Petter Ottersen, Mahmood Amiry-Moghaddam","doi":"10.1186/s12987-025-00676-3","DOIUrl":"10.1186/s12987-025-00676-3","url":null,"abstract":"<p><p>Aquaporin-4 (AQP4) is a key astrocytic water channel protein predominantly localized to perivascular endfeet, where it is believed to play a crucial role in brain fluid homeostasis and glymphatic waste clearance. Previous studies have suggested that the perivascular expression of AQP4 is regulated by circadian rhythms and peaks during the sleep phase, potentially influencing glymphatic function. However, direct evidence supporting circadian regulation of AQP4 remains limited. Here, we investigated AQP4 expression and perivascular distribution in the hippocampus and neocortex of mice at mid rest (day) and mid active phase (night). We employed quantitative immunogold electron microscopy (EM), in addition to immunofluorescence confocal microscopy, Western blotting, and qPCR to assess AQP4 localization and expression at the mRNA and protein levels. Our findings revealed no significant differences in AQP4 perivascular localization, total protein levels, or mRNA expression between day and night. Furthermore, the expression of key dystrophin-associated protein complex (DAPC) components, which anchor AQP4 to astrocytic endfeet, also remained largely unchanged. These results challenge the hypothesis that AQP4 localization is regulated by circadian rhythms and suggest that previously reported circadian differences in glymphatic function are mediated by factors other than AQP4 expression. This study highlights the need for further research into the mechanisms governing glymphatic function.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"64"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539670","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}
Sofia Behndig, Afroditi Lalou, Jan Axelsson, Jenny Larsson, Anders Wåhlin, Pavel Ryska, Ondrej Slezak, Katrine Riklund, Jan Zizka, Jan Malm, Anders Eklund
{"title":"qDESH: a method to quantify disproportionately enlarged subarachnoid space hydrocephalus.","authors":"Sofia Behndig, Afroditi Lalou, Jan Axelsson, Jenny Larsson, Anders Wåhlin, Pavel Ryska, Ondrej Slezak, Katrine Riklund, Jan Zizka, Jan Malm, Anders Eklund","doi":"10.1186/s12987-025-00677-2","DOIUrl":"10.1186/s12987-025-00677-2","url":null,"abstract":"<p><strong>Background and purpose: </strong>Disproportionately enlarged subarachnoid space hydrocephalus (DESH) is a radiological biomarker for idiopathic normal pressure hydrocephalus (iNPH). DESH is a subjective measure, based on visual assessments, which may limit its reliability. The aim of this study was to develop and validate a method for the objective quantification of DESH.</p><p><strong>Materials and methods: </strong>By using a semiautomatic quantitative method, we calculated quantitative DESH (qDESH), defined as a ratio between CSF volumes at high convexities and Sylvian fissures. The analysis was based on three-dimensional T1-weighted images from 35 subjects with iNPH (mean age 74 yrs; 10 females) and 45 controls (mean age 72 yrs; 13 females). The interrater agreement for qDESH was evaluated by the intraclass correlation coefficient, and qDESH was compared with visual assessments performed by two neuroradiologists.</p><p><strong>Results: </strong>All subjects with iNPH and 13% of the controls visually scored DESH positive. The median qDESH was 2.48 (5th to 95th percentile 0.88 to 5.42) for iNPH and 0.63 (5th to 95th percentile 0.37 to 1.73) for the controls. The area under the receiver operating characteristic curve for qDESH was 0.95 (95% confidence interval 0.90-1) in separating iNPH patients from controls. The interrater agreement for qDESH was 0.99 (95% CI 0.986-0.994, p < 0.001).</p><p><strong>Conclusion: </strong>Unlike visual DESH, qDESH generates a continuous variable, enabling reproducible quantification of DESH severity. With this method we can objectively investigate the diagnostic accuracy and prognostic assessment of DESH in iNPH.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"67"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539672","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":"Perivascular interactions and tissue properties modulate directional glymphatic transport in the brain.","authors":"Chenji Li, Sadegh Dabiri, Arezoo M Ardekani","doi":"10.1186/s12987-025-00668-3","DOIUrl":"10.1186/s12987-025-00668-3","url":null,"abstract":"<p><p>The glymphatic theory suggests a convective transport mechanism through brain tissue, which has significant implications for both brain waste clearance and drug delivery. However, the existence and driving mechanisms of directional convection from periarterial to perivenous spaces remain debated. Additionally, the role of brain tissue stiffness in parenchymal transport remains unclear, as experiments have reported varying trends in stiffness changes in cases of aging and neurodegenerative diseases. Previous mechanistic models often simplify or neglect perivenous spaces and venous deformation, raising questions about whether arterial vasomotion alone can effectively drive artery-to-vein transport. In this study, we propose a multiphysics model that incorporates the poroelastic nature of brain tissue, capturing the dynamic interactions between periarterial and perivenous spaces. Our results demonstrate that net glymphatic flow sweeps from periarterial space across parenchyma and is modulated by the periarterial-perivenous interactions, leading to higher pressure in periarterial space that drives unidirectional bulk transport from periarterial space to perivenous space. We also show that brain tissue stiffness presents a non-monotonic effect on both the glymphatic transport and its efficiency, with their respective peaks occurring at different stiffness values. Notably, the glymphatic convection rate peaks at physiologically relevant levels of brain stiffness. Furthermore, phase-delayed venous vasomotion is found to enhance glymphatic flow. These findings highlight the critical role of perivascular interactions and provide a framework for exploring brain fluid dynamics and potential therapeutic strategies for neurodegenerative diseases.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"63"},"PeriodicalIF":5.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474367","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 disorders and Alzheimer's disease: relationship and mechanisms involving neuroinflammation, orexin and Aβ.","authors":"Wenjing Zhang, Tenghong Lian, Mingyue He, Peng Guo, Huiying Guan, Jinghui Li, Jing Qi, Dongmei Luo, Jing Li, Yanan Zhang, Yue Huang, Gaifen Liu, Weijia Zhang, Zijing Zheng, Hao Yue, Zhan Liu, Fan Zhang, Ruidan Wang, Yao Meng, Wei Zhang","doi":"10.1186/s12987-025-00638-9","DOIUrl":"10.1186/s12987-025-00638-9","url":null,"abstract":"<p><strong>Aims: </strong>Sleep disorders are common in Alzheimer's disease (AD), but the underlying mechanisms are unknown. This study aimed to specifically investigate the relationship between a specific sleep disorder of short sleep duration (SSD) and AD, and related mechanisms involving neuroinflammation, orexin and AD biomarkers in both AD patients and mice.</p><p><strong>Methods: </strong>In part I, total 247 AD patients were consecutively recruited and categorized into AD with SSD (AD-SSD, < 6 h) and AD with no SSD (AD-nSSD, 7-8 h). Comparisons were made between the two groups in cognitive function, neuroinflammatory factors, orexinergic factors and AD biomarkers in cerebrospinal fluid (CSF). The correlations of orexinergic factors with the neuroinflammatory factors and AD biomarkers in CSF from AD-SSD group were investigated. In part II, the spatiotemporal relationships among glial activation, orexin expression, AD pathology, sleep architecture disturbance and cognitive function in 5XFAD mice were dynamically explored and the potential mechanisms underlying their relationships were analyzed.</p><p><strong>Results: </strong>In part I, compared to AD-nSSD group, AD-SSD group exhibited significantly poorer cognitive performance on the Montreal Cognitive Assessment and the Auditory Verbal Learning Test-delayed recall scales, higher orexin A level in CSF and lower β amyloid (Aβ) 42 level in CSF (all P < 0.05). Furthermore, orexin A had a positive correlation with prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) (r = 0.322, P = 0.002) and a negative correlation with Aβ42 (r = -0.223, P = 0.027) levels in CSF from AD-SSD group. In part II, compared with WT mice, 5XFAD mice displayed elevated hippocampal glial fibrillary acidic protein level at 3.5 months, increased hippocampal/cortical Chitinase-3-like protein 1 level, hypothalamic orexin A level and sleep architecture disturbance at 4.5 months, elevated insoluble Aβ42 deposition in hippocampus, orexinergic neuronal numbers in lateral hypothalamus, colocalization of their fibers with Aβ in cerebral cortex and cognitive impairment at 5.5 months old (all P < 0.05).</p><p><strong>Conclusion: </strong>SSD in AD is associated with significant cognitive impairment, neuroinflammation, orexin elevation and Aβ deposition. Hippocampal astroglial activation, hypothalamic orexin elevation and sleep architecture disturbance precede Aβ deposition in hippocampus and cognitive impairment in 5XFAD mice.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"62"},"PeriodicalIF":5.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336448","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}