{"title":"Choroid plexus modulates subventricular zone adult neurogenesis and olfaction through secretion of small extracellular vesicles.","authors":"Luke L Liu, Jonathan Shannahan, Wei Zheng","doi":"10.1186/s12987-026-00793-7","DOIUrl":"10.1186/s12987-026-00793-7","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590967","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}
Kardelen Akar, Lena Kollen, Hanna C Persson, Mats Tullberg
{"title":"Clinical characteristics and outcomes after shunt surgery in idiopathic normal pressure hydrocephalus with or without prior cerebrospinal fluid tap testing: a single-center follow-up study of 481 patients.","authors":"Kardelen Akar, Lena Kollen, Hanna C Persson, Mats Tullberg","doi":"10.1186/s12987-026-00802-9","DOIUrl":"10.1186/s12987-026-00802-9","url":null,"abstract":"<p><strong>Background: </strong>The cerebrospinal fluid tap test (CSF TT) is a commonly used predictive test for selecting patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery, but low sensitivity rate carries the risk of excluding individuals from effective treatment. We explored clinical characteristics and postoperative outcomes of iNPH patients shunted based solely on clinical and MRI findings compared with those shunted following a positive CSF TT.</p><p><strong>Methods: </strong>A total of 481 consecutive shunt operated iNPH patients were assessed in a team-based setting. Patients were categorized into two groups: those shunted based on typical clinical symptoms and MRI features without a supplementary test (NoTT, n = 390) and those shunted based on a positive CSF TT (TT, n = 91). Baseline clinical data, including comorbidities, and 5-month postoperative outcomes were assessed using the Gothenburg iNPH Scale and the modified Rankin scale (mRS).</p><p><strong>Results: </strong>Baseline characteristics and clinical measures were similar across groups, except that TT patients had more prevalent other concurrent neurological conditions (37% vs. 11%) and a longer delay between diagnosis and surgery (median 198 vs. 126 days) (both p < 0.001). Overall improvement (≥ 5-point postoperative increase in the total iNPH Scale) was observed in 70.9% of NoTT patients compared with 58.6% of TT patients (percentage point difference = 12.3; 95% CI = 0.3, 24.3; p = 0.044) while postoperative deterioration (defined as ≥ 5-point decrease on the iNPH Scale) was significantly more common in TT group (22.9%) than in the NoTT (10.7%) (percentage point difference = 12.1; 95% CI = 3.5, 20.7; p = 0.006). After adjusting for concurrent neurological disorder and surgical delay, improvement in continence (percentage point difference = 13.5, 95% CI = 0.7, 26.3) was better in NoTT patients (p = 0.039).</p><p><strong>Conclusions: </strong>This real-world study shows that a majority of iNPH patients can be routinely assessed by a clinical team and shunted with favorable outcomes without a supplementary predictive tap test. The worse outcomes seen in TT patients are likely to be due to higher prevalence of neurological comorbidity and delayed time to surgery. We suggest that the tap test may be reserved for difficult patients with suspected iNPH including those who present with concurrent other neurological disorders.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591001","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}
Ayk Waldow, Andreas Brachner, Nicolas Perriere, Winfried Neuhaus, Jörg Piontek
{"title":"Nanoscopic analysis of tight junction organization in in vitro blood-brain barrier models.","authors":"Ayk Waldow, Andreas Brachner, Nicolas Perriere, Winfried Neuhaus, Jörg Piontek","doi":"10.1186/s12987-026-00799-1","DOIUrl":"10.1186/s12987-026-00799-1","url":null,"abstract":"<p><strong>Background: </strong>The composition of tight junctions (TJs) in epithelia is well understood, whereas that one in endothelial cells at the blood-brain barrier (BBB) is controversial. Although freeze fracture EM remains the gold standard for assessing TJ nano-structures, advances in fluorescence microscopy, such as stimulated emission depletion (STED) together with image analysis tools, allow immunostaining-based quantitative analysis of the protein composition and the nano-organization of TJ strands.</p><p><strong>Methods: </strong>Here, we present two approaches for quantitative analysis of the BBB TJ meshwork utilizing confocal and STED imaging together with open access image analysis tools CellProfiler, iLastik and ImageJ. For the first use case, a BBB model based on brain capillary endothelial-like cells (BCELCs) differentiated from human induced pluripotent stem cells (hiPSC) was employed. For the second one, monolayers of human primary brain microvascular endothelial cells (pBMVECs) were used.</p><p><strong>Results: </strong>STED analysis of BCELC monolayers revealed that here claudin-5 co-polymerizes with claudin-4 and - 6 into continuous TJ strand meshworks. Treatments with established TJ openers (1.4 M mannitol or C. perfringens enterotoxin-based claudin binders) strongly decreased transendothelial resistance (TEER) accompanied by a reduction in the nanoscopic co-localization of claudin-5/-4, -5/-6 and amount of junctional claudin-5. These findings suggested that in hiPSC-based BBB models multiple claudins together constitute TJs, leading to a tight paracellular barrier against solutes. Using STED imaging of pBMVECs immunostained for Cldn5, extensive meshworks of continuous TJ strands were detected. In contrast to the hiPSC-based model, other claudins were not detected. TEER and morphometric analyses of Cldn5-positive strands revealed that the barrier defect caused by claudin-5 binders is due to impaired TJ structural integrity.</p><p><strong>Conclusions: </strong>The findings suggest that Cldn5 is sufficient to form the tight paracellular barrier at the BBB. The presence of claudin-4, -5 and - 6 in hiPSC-derived cells reflects a mixed phenotype depending on their differentiation process. In sum, we demonstrated that, unlike confocal imaging, STED enables monitoring the composition and structural integrity of BBB TJ strands.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147591006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke.","authors":"Tamara Etuzé, Louis Fosset, Denis Vivien, Benoit Denis Roussel, Eloise Lemarchand","doi":"10.1186/s12987-026-00801-w","DOIUrl":"10.1186/s12987-026-00801-w","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is one of the leading causes of death and disability worldwide and thrombolysis, with tissue-type plasminogen activator (tPA) or its mutants, remains the only pharmacological treatment available for the acute phase. In this study, we hypothesised that endothelial tPA plays a key role in modulating the microglial response and maintaining blood brain barrier (BBB) integrity after stroke.</p><p><strong>Methods: </strong>Using a mouse model with endothelial-specific deletion of tPA (VeCad<sup>Cre</sup> - tPA<sup>Flox</sup>), combined with a thrombotic stroke model and high-resolution imaging, we investigated the effects of endothelial tPA on vascular inflammation and microglial activation.</p><p><strong>Results: </strong>Our results demonstrate that microglia-vessel contacts increase post-stroke. Notably, deletion of endothelial tPA reduces vascular cell adhesion molecule 1 (VCAM1) expression and is associated with decreased microglial activation and fewer microglia-vessel contacts. Interestingly, endothelial tPA deletion also leads to increased BBB permeability and a heightened risk of haemorrhagic transformation following stroke.</p><p><strong>Conclusions: </strong>Collectively, these findings indicate that endothelial tPA promotes microglial recruitment to blood vessels and plays a protective role in preserving BBB integrity after ischemic stroke.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573008","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}
Paula Gimenez, Rohisha T Shakya, Fidel Santamaria, Jan Tønnesen
{"title":"Extracellular space diffusion modelling identifies distinct functional advantages of glutamatergic and GABAergic synapse geometries.","authors":"Paula Gimenez, Rohisha T Shakya, Fidel Santamaria, Jan Tønnesen","doi":"10.1186/s12987-026-00797-3","DOIUrl":"10.1186/s12987-026-00797-3","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510929","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":"TRPV4 inhibition as a pharmacotherapy for post-hemorrhagic hydrocephalus.","authors":"Trine L Toft-Bertelsen, Nanna MacAulay","doi":"10.1186/s12987-026-00790-w","DOIUrl":"10.1186/s12987-026-00790-w","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510946","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}
Sarah Joost, Hannes Kaddatz, Elise Vankriekelsvenne, Lars-Ove Brandenburg
{"title":"The meninges as a neuroimmune interface: structure, barriers and roles in CNS disease.","authors":"Sarah Joost, Hannes Kaddatz, Elise Vankriekelsvenne, Lars-Ove Brandenburg","doi":"10.1186/s12987-026-00795-5","DOIUrl":"10.1186/s12987-026-00795-5","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473101","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}
Christopher W Roberts, Brandon G Rocque, Leopold Arko Iv, Neena I Marupudi, Sandeep Sood, Elise Yoon, Elliot Widd, Bryn A Martin, Carolyn A Harris
{"title":"Role of cerebroventricular size and surgical placement in modulating catheter flow distribution.","authors":"Christopher W Roberts, Brandon G Rocque, Leopold Arko Iv, Neena I Marupudi, Sandeep Sood, Elise Yoon, Elliot Widd, Bryn A Martin, Carolyn A Harris","doi":"10.1186/s12987-026-00786-6","DOIUrl":"10.1186/s12987-026-00786-6","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473135","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: Reducing assessment timing in Tap-Test-positive patients with iNPH: a 24-hour strategy and the exploratory role of the Symbol-Digit Modalities Test in surgical triage.","authors":"Zeyi Yang, Zi'ang Geng, Rui Yin, Congcong Deng, Sishuai Sun, Pengtao Li, Yihao Chen, Xiaoyu Liu, Ziyuan Fang, Yue Wang, Xiao Zhang, Liling Dong, Chenhui Mao, Jing Gao, Junji Wei","doi":"10.1186/s12987-026-00792-8","DOIUrl":"10.1186/s12987-026-00792-8","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467156","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}