Leonardo A Rivera-Rivera, Bruce Collick, Tomas Vikner, Sterling C Johnson, Kevin M Johnson
{"title":"Synchronous quantification of arterial, venous, and cerebrospinal fluid flow dynamics using real-time phase-contrast MRI.","authors":"Leonardo A Rivera-Rivera, Bruce Collick, Tomas Vikner, Sterling C Johnson, Kevin M Johnson","doi":"10.1186/s12987-025-00722-0","DOIUrl":"10.1186/s12987-025-00722-0","url":null,"abstract":"<p><strong>Background: </strong>Neurofluid flow dynamics are frequently studied from asynchronous blood and CSF flow measurements from real-time imaging using separate phase contrast (PC) MRI scans. Asynchronous measures can be influenced by changes in heart rate, respiration, and other physiological processes, obfuscating neurofluids assessment. Here we present an approach for synchronous measures of neurofluids using simultaneous real-time 2D PC MRI and investigated the effects of different breathing patterns on synchronous and asynchronous blood and CSF flow in a group of healthy participants.</p><p><strong>Methods: </strong>Interleaved dual-velocity encoding 2D PC MRI with retrospective real-time reconstruction was utilized for synchronous neurofluid measures during free breathing, paced breathing and breath holds. Data were collected on a clinical 3.0T scanner at the level of C1/C2 vertebrae in 10 participants. From real-time images, flow rates repeated measures, and cardiac and respiratory flow power were assessed using Bland-Altman, power spectral analyses, and breathing pattern group differences. Neurofluids coupling from cross-correlation between arterial and venous blood and CSF flow signals were quantified from synchronous and asynchronous measures. Real-time images were re-binned to the cardiac cycle and compared to high-temporal resolution cardiac-resolved images in terms of flow rate, pulsatility index, and stroke volume.</p><p><strong>Results: </strong>Flow repeatability was highest in free breathing scans and in arteries and spinal canal compared to veins from Bland-Altman and repeatability coefficients. Significant differences were measured in cardiac and respiratory flow power across breathing patterns in various vessel segments and spinal canal (P ≤ 0.006). Synchronous blood and CSF cardiac coupling were significantly higher than asynchronous results in all vessels (P = 0.002). For example, free breathing synchronous cardiac couplings ranged from [0.81, 0.93], compared to asynchronous range [0.49, 0.53]. Synchronous cardiac coupling showed significant differences across breathing patterns in most vessels (P = 0.002). Comparison between real-time cardiac re-binned images and high-temporal resolution cardiac-resolved images showed high correlations for flow rate and spinal canal stroke volume (ρ ≥ 0.95) and lower for pulsatility index (ρ = [0.45, 0.88]).</p><p><strong>Conclusions: </strong>Breathing patterns induced significant responses across neurofluids including in flow rates, flow power, and coupling parameters. Higher cross-correlation among synchronous measures support benefits over asynchronous measures for neurofluids coupling characterization.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"108"},"PeriodicalIF":6.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388342","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}
Yangjie Li, Ying Cai, Kangling Xie, Fan Hu, Jiaohao Li, Cui Li, Runjie Zhang, Zhengwei Zhong
{"title":"Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.","authors":"Yangjie Li, Ying Cai, Kangling Xie, Fan Hu, Jiaohao Li, Cui Li, Runjie Zhang, Zhengwei Zhong","doi":"10.1186/s12987-025-00713-1","DOIUrl":"10.1186/s12987-025-00713-1","url":null,"abstract":"<p><p>Cerebral small vessel disease (CSVD) encompasses diffuse brain lesions arising from structural injury to small vessels, and is closely associated with chronic hypoperfusion and blood-brain barrier (BBB) dysfunction. Its insidious onset and heterogeneous clinical manifestations render elucidation of its pathogenesis and development of targeted interventions of paramount clinical importance. Transforming growth factorβ (TGFβ), a pivotal regulator of vascular homeostasis, exerts bidirectional effects within the neurovascular unit (NVU) during CSVD: under physiological conditions, TGFβ maintains barrier integrity by modulating endothelial tight junction proteins and pericyte adhesion; under pathological stress, dysregulated TGFβ signaling induces endothelial dysfunction, pericyte degeneration and neuroinflammation, thereby promoting white-matter injury. Precise, spatiotemporal modulation of TGFβ pathways therefore represents a promising avenue for stage-specific, molecularly targeted therapy in CSVD.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"107"},"PeriodicalIF":6.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388320","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":"White matter lesions associated with the reemergence of grasp reflexes in patients with idiopathic normal pressure hydrocephalus.","authors":"Junyan Liu, Shigenori Kanno, Chifumi Iseki, Nobuko Kawakami, Kazuo Kakinuma, Kazuto Katsuse, Shiho Matsubara, Shoko Ota, Keiko Endo, Kentaro Takanami, Shin-Ichiro Osawa, Tomohiro Kawaguchi, Hidenori Endo, Shunji Mugikura, Kyoko Suzuki","doi":"10.1186/s12987-025-00718-w","DOIUrl":"10.1186/s12987-025-00718-w","url":null,"abstract":"<p><strong>Background: </strong>The white matter damage inducing the reemergence of grasp reflexes and their potential lateralization remains unstudied. Idiopathic normal pressure hydrocephalus (iNPH), a subcortical dementia, is an ideal model for these investigations. We aim to understand the contributions of white matter to the inhibition of grasp reflexes in patients with iNPH.</p><p><strong>Methods: </strong>A total of 48 patients (mean age at admission: 77.8 ± 5.2 years; 56% male) with probable iNPH were retrospectively enrolled in this study. The intensity of grasp reflexes was assessed using a four-category classification. A voxel-based morphometric analysis of the fractional anisotropy (FA) maps was conducted to identify responsible regions related to the grasp reflex. The white matter fibers passing through these regions were tracked using fiber-tracking data from fifty age-/sex-matched healthy subjects from the Lifespan Human Connectome Project Aging Study. Fibers with an inter-subject overlap rate > 50% were defined as reliable tracts for further discussion.</p><p><strong>Results: </strong>Positive grasp reflex was identified in 60% (29/48) of probable iNPH cases. The voxel-based multiple regression analysis revealed that the reflex intensity scores were negatively correlated with FA values in the right frontal subcortical white matter near the anterior horn of the right lateral ventricle. The white matter fibers project through this structure mainly to the posterior parts of the right superior, middle, and inferior frontal gyri; the bilateral presupplementary motor areas; the right dorsal anterior cingulate cortex; the ventral lateral nuclei of the bilateral thalami; the pulvinar inferior nucleus of the right thalamus; the lateral part of the right putamen; and the right subthalamic nucleus.</p><p><strong>Conclusion: </strong>The inhibition of grasp reflexes is achieved via a right-lateralized prefrontal cortex-basal ganglia-thalamocortical 'stopping' network.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"106"},"PeriodicalIF":6.2,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12557853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376793","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":"Reply to Comment by Quistorff: ATP is not consumed solely by hydrolytic reactions.","authors":"Gerald A Dienel, Martin Lauritzen","doi":"10.1186/s12987-025-00711-3","DOIUrl":"10.1186/s12987-025-00711-3","url":null,"abstract":"<p><p>A Comment to our recent paper that described a budget for brain metabolic water production claimed that all ATP produced by oxidation of glucose is consumed by hydrolysis, and that the net calculated production of metabolic water is equal to that obtained by combustion of glucose. However, ATP is synthesized and consumed by enzymatic reactions that do not involve water in the mechanism. Not all ATP consumed is hydrolyzed.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"105"},"PeriodicalIF":6.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354274","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":"Formation of metabolic water by aerobic glucose oxidation.","authors":"Bjørn Quistorff","doi":"10.1186/s12987-025-00712-2","DOIUrl":"10.1186/s12987-025-00712-2","url":null,"abstract":"<p><p>A recent paper suggests that the water originating from the ATP production coupled to aerobic glucose oxidation causes more than a 6 fold increase in the production of metabolic water, compared with the standard textbook description of the oxidation process. However, the authors seem to have forgotten that the simultaneous processes of ATP utilization takes up the same amount of water, which was liberated during the ATP synthesis. Thus, at steady state, there is no net increase in the production of metabolic water.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"104"},"PeriodicalIF":6.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354248","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}
Erin C Reardon, Aisling J Greaney, John J E Mulvihill
{"title":"From glia limitans to glial scars: in vitro co-culture studies of the astrocyte and meningeal interaction.","authors":"Erin C Reardon, Aisling J Greaney, John J E Mulvihill","doi":"10.1186/s12987-025-00715-z","DOIUrl":"10.1186/s12987-025-00715-z","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"103"},"PeriodicalIF":6.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344281","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}
Joshua P Koleske, Shelei Pan, Thanda Meehan, Maren Loe, Diego M Morales, Brendan P Lucey, Erik Musiek, Jennifer M Strahle
{"title":"Time-of-day and age-related patterns in cerebrospinal fluid glucose and protein.","authors":"Joshua P Koleske, Shelei Pan, Thanda Meehan, Maren Loe, Diego M Morales, Brendan P Lucey, Erik Musiek, Jennifer M Strahle","doi":"10.1186/s12987-025-00686-1","DOIUrl":"10.1186/s12987-025-00686-1","url":null,"abstract":"<p><strong>Background: </strong>Known circadian variations in cerebrospinal fluid (CSF) flow and composition include fluctuations in electrolytes, hormones, and neurotransmitters. However, how commonly measured CSF constituents, such as protein and glucose, vary by time-of-day is understudied. Here, we identify and compare time-of-day differences in CSF protein and glucose from patients who underwent CSF collection during clinical care.</p><p><strong>Methods: </strong>Patients with CSF collected between June 2018 and May 2023 at thirteen hospitals within our institution's health system were identified. Clinical, demographic and laboratory results were recorded. CSF results were divided into 1- and 4-hour intervals based on time-of-day and patient age. Patients were excluded if there was evidence of CSF infection, bleeding, as well as age criteria excluding neonates. One-way ANOVA with post-hoc Tukey was used to analyze differences between means.</p><p><strong>Results: </strong>15,272 patients underwent 26,397 CSF collection encounters. After exclusion, 8,210 CSF glucose and 10,103 CSF protein values remained. The CSF/blood glucose ratio showed time-of-day fluctuations; the mean ratio was higher from 00:00-04:00 (0.660), 04:00-08:00 (0.651), 16:00-20:00 (0.619), and 20:00-00:00 (0.633) than from 08:00-12:00 (0.588) and 12:00-16:00 (0.599). This pattern was also observed when dividing the time-of-day into 1-hour intervals and in every age cohort except patients 80 years and older. Children also exhibited time-of-day differences in CSF/blood glucose ratios, but the phase of their time-of-day pattern is shifted earlier to peak at 00:00-04:00. No clear time-of-day patterns were observed for CSF protein; however there was a significant association of age with CSF protein (R<sup>2</sup> = 0.2182). There were no meaningful differences in CSF protein by time-of-day after separating patients by age.</p><p><strong>Conclusions: </strong>Higher CSF glucose from 00:00-08:00 and 16:00-00:00 compared to 08:00-16:00 suggests diurnal fluctuations which may be driven by a circadian rhythm. A higher CSF protein concentration was strongly associated with increasing age, without clear time-of-day variations. These results have implications for clinical interpretation and future research of the role of CSF in health and disease.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"102"},"PeriodicalIF":6.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307428","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}
Sera N Ganearachchi, Brianna C Afiat, Pei Ying Lee, Anh Hoang, Christine T O Nguyen, Peter Wostyn, Bang V Bui, Da Zhao
{"title":"Effect of intracerebral infusion rate on optic nerve tissue pressure and diurnal intracranial pressure in rats.","authors":"Sera N Ganearachchi, Brianna C Afiat, Pei Ying Lee, Anh Hoang, Christine T O Nguyen, Peter Wostyn, Bang V Bui, Da Zhao","doi":"10.1186/s12987-025-00714-0","DOIUrl":"10.1186/s12987-025-00714-0","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"100"},"PeriodicalIF":6.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291720","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}
Xinyi Zhou, Sofía García Del Barrio Cervera, Yuanqi Sun, Yinghao Li, Wei Li, Licia Pacheco-Luna, Haris I Sair, Adrian Paez, Linda Knutsson, Peter C M van Zijl, Vidyulata Kamath, Arnold Bakker, Bryan K Ward, Jun Hua
{"title":"Imaging the distribution and drainage of fluid in the human olfactory regions using intravenous Gadolinium-based contrast agents (GBCA) enhanced MRI.","authors":"Xinyi Zhou, Sofía García Del Barrio Cervera, Yuanqi Sun, Yinghao Li, Wei Li, Licia Pacheco-Luna, Haris I Sair, Adrian Paez, Linda Knutsson, Peter C M van Zijl, Vidyulata Kamath, Arnold Bakker, Bryan K Ward, Jun Hua","doi":"10.1186/s12987-025-00710-4","DOIUrl":"10.1186/s12987-025-00710-4","url":null,"abstract":"<p><strong>Background: </strong>Cerebrospinal fluid (CSF) clearance via the olfactory pathway is well-documented in animal models. However, results from in vivo human studies appear inconsistent. Studies using intrathecal (IT) Gadolinium-based contrast agents (GBCA) enhanced MRI showed minimal tracer pass-through from intracranial to extracranial olfactory regions such as the nasal mucosa. Conversely, human imaging studies using intravenous (IV) tracers showed significant enhancement in the nasal mucosa, suggesting CSF drainage through the cribriform plate. This research seeks to clarify these conflicting results from imaging studies using intrathecal and intravenous tracers, and to provide a better understanding of intravenous GBCA distribution in intracranial and extracranial olfactory regions, an important issue for studies using intravenous-GBCA-enhanced-MRI to investigate CSF clearance.</p><p><strong>Methods: </strong>Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was applied to measure GBCA distribution in the CSF immediately and 4 h after intravenous administration in 25 healthy volunteers (48.9 ± 19.5 years; 14 females). A region-of-interest (ROI)-based and a voxel-based analysis were performed to measure GBCA concentration in intracranial and extracranial olfactory regions. Paired t-tests were used to compare pre- and post-GBCA signal changes.</p><p><strong>Results: </strong>GBCA-induced signal changes were detected in all olfactory regions immediately and 4 h after intravenous GBCA administration. GBCA concentration was significantly greater (P < 0.01) in extracranial olfactory regions than intracranial olfactory regions. At 4 h post-GBCA, GBCA concentration decreased in extracranial olfactory regions compared to the immediate post-GBCA period, while it was comparable at both time points in intracranial olfactory regions.</p><p><strong>Conclusions: </strong>Intravenous-GBCA-enhanced-MRI can detect GBCA distribution in the CSF space of olfactory regions in healthy subjects. The GBCA-induced CSF signal changes in intracranial olfactory regions were substantially smaller compared to extracranial olfactory regions. GBCA concentration in the CSF of intracranial olfactory regions was comparable to other intracranial regions. The significant GBCA-induced signal changes in extracranial olfactory regions may largely originate from peripheral blood supply when using intravenous tracers, which reflects lymphatic fluid circulation in the extracranial lymphatic system, and are not directly related to CSF clearance from the brain. Therefore, when using intravenous tracer-based imaging methods, it is critical to separate intracranial and extracranial regions in the analysis due to their different vascular supply.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"101"},"PeriodicalIF":6.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291766","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}
Irum Naureen, Khawaja A Irfan Waheed, Ahsen W Rathore, Suresh Victor, Conor Mallucci, John R Goodden, Shahid N Chohan, Jaleel A Miyan
{"title":"Correction: Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: glial proteins associated with cell damage and loss.","authors":"Irum Naureen, Khawaja A Irfan Waheed, Ahsen W Rathore, Suresh Victor, Conor Mallucci, John R Goodden, Shahid N Chohan, Jaleel A Miyan","doi":"10.1186/s12987-025-00703-3","DOIUrl":"10.1186/s12987-025-00703-3","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"99"},"PeriodicalIF":6.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257696","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}