Fluids and Barriers of the CNS最新文献

{"title":"Breaking boundaries: role of the brain barriers in metastatic process.","authors":"Nasim Izadi, Peter Solár, Klaudia Hašanová, Alemeh Zamani, Maryam Shahidian Akbar, Klára Mrázová, Martin Bartošík, Tomáš Kazda, Roman Hrstka, Marek Joukal","doi":"10.1186/s12987-025-00618-z","DOIUrl":"10.1186/s12987-025-00618-z","url":null,"abstract":"<p><p>Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently. The metastatic cascade is a multistep process involving local invasion, intravasation into the bloodstream or lymphatic system, extravasation into normal tissue, and colonization of the distal site. After reaching the brain, circulating tumor cells (CTCs) breach the blood-brain barrier (BBB).The selective permeability of the BBB poses a significant challenge for therapeutic compounds, limiting the treatment efficacy of BMs. Understanding the mechanisms of tumor cell interactions with the BBB is crucial for the development of effective treatments. This review provides an in-depth analysis of the brain barriers, including the BBB, blood-spinal cord barrier, blood-meningeal barrier, blood-arachnoid barrier, and blood-cerebrospinal fluid barrier. It explores the molecular and cellular components of these barriers and their roles in brain metastasis, highlighting the importance of this knowledge for identifying druggable targets to prevent or limit BM formation.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"3"},"PeriodicalIF":5.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947096","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: Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood-brain barrier.","authors":"Joanna R Thomas, William J E Frye, Robert W Robey, Andrew C Warner, Donna Butcher, Jennifer L Matta, Tamara C Morgan, Elijah F Edmondson, Paula B Salazar, Suresh V Ambudkar, Michael M Gottesman","doi":"10.1186/s12987-024-00606-9","DOIUrl":"10.1186/s12987-024-00606-9","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"2"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926613","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":"Transmantle pressure under the influence of free breathing: non-invasive quantification of the aqueduct pressure gradient in healthy adults.","authors":"Pan Liu, Kimi Owashi, Heimiri Monnier, Serge Metanbou, Cyrille Capel, Olivier Balédent","doi":"10.1186/s12987-024-00612-x","DOIUrl":"https://doi.org/10.1186/s12987-024-00612-x","url":null,"abstract":"<p><strong>Background: </strong>The pressure gradient between the ventricles and the subarachnoid space (transmantle pressure) is crucial for understanding CSF circulation and the pathogenesis of certain neurodegenerative diseases. This pressure can be approximated by the pressure difference across the aqueduct (ΔP). Currently, no dedicated platform exists for quantifying ΔP, and no research has been conducted on the impact of breathing on ΔP. This study aims to develop a post-processing platform that balances accuracy and ease of use to quantify aqueduct resistance and, in combination with real-time phase contrast MRI, quantify ΔP driven by free breathing and cardiac activities.</p><p><strong>Methods: </strong>Thirty-four healthy participants underwent 3D balanced fast field echo (BFFE) sequence and real-time phase contrast (RT-PC) imaging on a 3T scanner. We used the developed post-processing platform to analyse the BFFE images to quantify the aqueduct morphological parameters such as resistance. RT-PC data were then processed to quantify peak flow rates driven by cardiac and free breathing activity (Qc and Qb) in both directions. By multiplying these Q by resistance, ΔP driven by cardiac and breathing activity was obtained (ΔPc and ΔPb). The relationships between aqueduct resistance and flow rates and ΔP driven by cardiac and breathing activity were analysed, including a sex difference analysis.</p><p><strong>Results: </strong>The aqueduct resistance was 78 ± 51 mPa·s/mm³. The peak-to-peak cardiac-driven ΔP (Sum of ΔPc⁺ and ΔPc^-) was 24.2 ± 11.4 Pa, i.e., 0.18 ± 0.09 mmHg. The peak-to-peak breath-driven ΔP was 19 ± 14.4 Pa, i.e., 0.14 ± 0.11 mmHg. Males had a longer aqueduct than females (17.9 ± 3.1 mm vs. 15 ± 2.5 mm, p < 0.01) and a larger average diameter (2.0 ± 0.2 mm vs. 1.8 ± 0.3 mm, p = 0.024), but there was no gender difference in resistance values (p = 0.25). Aqueduct resistance was negatively correlated with stroke volume and the peak cardiac-driven flow (p < 0.05); however, there was no correlation between aqueduct resistance and breath-driven peak flow rate.</p><p><strong>Conclusions: </strong>The highly automated post-processing software developed in this study effectively balances ease of use and accuracy for quantifying aqueduct resistance, providing technical support for future research on cerebral circulation physiology and the exploration of new clinical diagnostic methods. By integrating real-time phase contrast MRI, this study is the first to quantify the aqueduct pressure difference under the influence of free breathing. This provides an important physiological reference for further studies on the impact of breathing on transmantle pressure and cerebral circulation mechanisms.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"1"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926748","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":"Research priorities for improving cognitive and neuropsychological outcomes in hydrocephalus.","authors":"Nickolas Dasher, T Andrew Zabel, Maria Garcia-Bonilla, Lauren L Jantzie, Mark G Hamilton, Michael A Williams, Monica J Chau","doi":"10.1186/s12987-024-00602-z","DOIUrl":"10.1186/s12987-024-00602-z","url":null,"abstract":"<p><p>Hydrocephalus is a neurological disorder that impacts approximately 85 per 100,000 individuals worldwide and is associated with motor and cognitive impairments. While many advances in surgical interventions have helped substantially improve the survival rates and quality of life of those affected, there continues to be significant gaps in our understanding of the etiology of this heterogeneous condition as well as its specific neuropsychological and functional challenges across different phases of life. To address these limitations, the Hydrocephalus Association and Rudi Schulte Research Institute organized a workshop titled, \"Improving Cognitive and Psychological Outcomes in Hydrocephalus\", composed of top academics in the fields of hydrocephalus, cognition, and neuropsychology, as well as individuals with hydrocephalus or their caregivers. The purpose was to review the available evidence and propose pertinent areas of further research to improve the cognitive functioning, functional status, and quality of life of individuals with hydrocephalus. These topics included cognitive and neuropsychological assessments and daily-life function of children and adults living with hydrocephalus, biomarkers of cognitive function, animal modeling of hydrocephalus, and the longitudinal impact of hydrocephalus treatment. The following paper outlines four primary areas that warrant research: (1) neuropsychological phenotypes, (2) treatment-focused research considerations, (3) translational pre-clinical tools, and (4) establishing pathways for longitudinal care. Through the efforts of this group, the goal of this manuscript is to inspire and direct scientific and clinical inquiry towards these noted research priorities to further improve the lives of individuals with hydrocephalus and their families.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"109"},"PeriodicalIF":5.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909371","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 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/s12987-024-00611-y","DOIUrl":"10.1186/s12987-024-00611-y","url":null,"abstract":"<p><strong>Background: </strong>Disproportionately enlarged subarachnoid space hydrocephalus (DESH) is one of the neuroradiological characteristics of idiopathic normal pressure hydrocephalus (iNPH), which makes statistical analyses of brain images difficult. This study aimed to develop and validate methods of accurate brain segmentation and spatial normalisation in patients with DESH by using the Computational Anatomy Toolbox (CAT12).</p><p><strong>Methods: </strong>Two hundred ninety-eight iNPH patients with DESH and 25 healthy controls (HCs) who underwent cranial MRI were enrolled in this study. We selected the structural images of 169 patients to create customised tissue probability maps and diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) templates for patients with DESH (DESH-TPM and DESH-Template). The structural images of 38 other patients were used to evaluate the validity of the DESH-TPM and DESH-Template. DESH-TPM and DESH-Template were created using the 114 well-segmented images after the segmentation processing of CAT12. In the validation study, we compared the accuracy of brain segmentation and spatial normalisation among three conditions: customised condition, applying DESH-TPM and DESH-Template to CAT12 and patient images; standard condition, applying the default setting of CAT12 to patient images; and reference condition, applying the default setting of CAT12 to HC images.</p><p><strong>Results: </strong>In the validation study, we identified three error types during segmentation. (1) The proportions of misidentifying the dura and/or extradural structures as brain structures in the customised, standard, and reference conditions were 10.5%, 44.7%, and 13.6%, respectively; (2) the failure rates of white matter hypointensity (WMH) cancellation in the customised, standard, and reference conditions were 18.4%, 44.7%, and 0%, respectively; and (3) the proportions of cerebrospinal fluid (CSF)-image deficits in the customised, standard, and reference conditions were 97.4%, 84.2%, and 28%, respectively. The spatial normalisation accuracy of grey and white matter images in the customised condition was the highest among the three conditions, especially in terms of superior convexity.</p><p><strong>Conclusions: </strong>Applying the combination of the DESH-TPM and DESH-Template to CAT12 could improve the accuracy of grey and white matter segmentation and spatial normalisation in patients with DESH. However, this combination could not improve the CSF segmentation accuracy. Another approach is needed to overcome this challenge.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"108"},"PeriodicalIF":5.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906782","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":"BOLD-CSF dynamics assessed using real-time phase contrast CSF flow interleaved with cortical BOLD MRI.","authors":"Emiel C A Roefs, Ingmar Eiling, Jeroen de Bresser, Matthias J P van Osch, Lydiane Hirschler","doi":"10.1186/s12987-024-00607-8","DOIUrl":"10.1186/s12987-024-00607-8","url":null,"abstract":"<p><strong>Background: </strong>Cerebrospinal fluid (CSF) motion and pulsatility has been proposed to play a crucial role in clearing brain waste. Although its driving forces remain debated, increasing evidence suggests that large amplitude vasomotion drives such CSF fluctuations. Recently, a fast blood-oxygen-level-dependent (BOLD) fMRI sequence was used to measure the coupling between CSF fluctuations and low-frequency hemodynamic oscillations in the human cortex. However, this technique is not quantitative, only captures unidirectional flow and is sensitive to B0-fluctuations. Real-time phase contrast (pcCSF) instead measures CSF flow dynamics in a fast, quantitative, bidirectional and B0-insensitive manner, but lacks information on hemodynamic brain oscillations. In this study we propose to combine the strengths of both sequences by interleaving real-time phase contrast with a cortical BOLD scan, thereby enabling the quantification of the interaction between CSF flow and cortical BOLD.</p><p><strong>Methods: </strong>Two experiments were performed. First, we compared the CSF flow measured using real-time phase contrast (pcCSF) with the inflow-sensitized BOLD (iCSF) measurements by interleaving both techniques at the repetition level and planning them at the same location. Next, we compared the BOLD-CSF coupling obtained using the novel pcCSF interleaved with cortical BOLD to the coupling obtained with the original iCSF. To time-lock the CSF fluctuations, participants were instructed to perform slow, abdominal paced breathing.</p><p><strong>Results: </strong>pcCSF captures bidirectional CSF dynamics with a more pronounced in- and outflow curve than the original iCSF method. With the pcCSF method, the BOLD-CSF coupling was stronger (mean cross-correlation peak increase = 0.22, p = .008) and with a 1.9 s shorter temporal lag (p = .016), as compared to using the original iCSF technique.</p><p><strong>Conclusions: </strong>In this study, we introduce a new method to study the coupling of CSF flow measured in the fourth ventricle to cortical BOLD fluctuations. In contrast to the original approach, the use of phase contrast MRI to measure CSF flow provides a quantitative in- and outflow curve, and improved BOLD-CSF coupling metrics.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"107"},"PeriodicalIF":5.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885368","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":"In response to Mutti et al. 2024 commentary on \"Transient intracranial pressure elevations (B waves) associated with sleep apnea: the neglected role of cyclic alternating pattern\".","authors":"Casper Schwartz Riedel","doi":"10.1186/s12987-024-00610-z","DOIUrl":"10.1186/s12987-024-00610-z","url":null,"abstract":"<p><p>The physiology of transient intracranial pressure (ICP) elevations (B waves), remains incompletely understood and appears to involve multiple mechanisms, including obstructive sleep apnea (OSA). Transient ICP elevations are associated with OSA and cyclic alternating pattern (CAP) metrics, suggesting a complex interplay between sleep fragmentation and ICP dynamics. Additionally, CAP metrics could complement standard OSA assessments, providing deeper insights into transient ICP fluctuations, particularly in conditions like normal-pressure hydrocephalus and idiopathic intracranial hypertension. Future studies should explore CAP-ICP interactions to elucidate their physiological and clinical implications.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"105"},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863732","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":"Recapitulation of physiologic and pathophysiologic pulsatile CSF flow in purpose-built high-throughput hydrocephalus bioreactors.","authors":"Ahmad Faryami, Adam Menkara, Shaheer Ajaz, Christopher Roberts, Ryan Jaroudi, Blake Gura, Tala Hussini, Carolyn A Harris","doi":"10.1186/s12987-024-00600-1","DOIUrl":"10.1186/s12987-024-00600-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hydrocephalus, an accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain, is often treated via a shunt system to divert the excess CSF to a different compartment; if left untreated, it can lead to serious complications and permanent brain damage. It is estimated that one in every 500 people are born with hydrocephalus. Despite more than 60 years of concerted efforts, shunts still have the highest failure rate of any neurological device requiring follow-up shunt revision surgeries and contributing to the $2 billion cost of hydrocephalus care in the US alone. The absence of a tested and validated long-term in-vitro model that can incorporate clinically relevant parameters has limited hypothesis-driven studies and, in turn, limited our progress in understanding the mechanisms of shunt obstruction in hydrocephalus. Testing clinical parameters of flow, pressure, shear, catheter material, surface modifications, and others while optimizing for minimal protein, cellular, and blood interactions has yet to be done systematically for ventricular catheters. Several studies point to the need to not only understand how cells and tissues have occluded these shunt catheters but also how to stop the likely multi-faceted failure. For instance, studies show us that tissue occluding the ventricular catheter is primarily composed of proliferating astrocytes and cells of the macrophage lineage. Cell reactivity has been observed to follow flow gradients, with elevated levels of typically pro-inflammatory interleukin-6 produced under shear stress conditions greater than 0.5 dyne/[Formula: see text]. But also, that shear can shift cellular attachment. The Automated, In vitro Model for hydrocephalus research (AIMS), presented here, improves upon our previous long-term in vitro systems with specific goals of recapitulating bulk pulsatile cerebrospinal fluid (CSF) waveforms and steady-state flow directionality relevant to ventricular catheters used in hydrocephalus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The AIMS setup was developed to recapitulate a wide range of physiologic and pathophysiologic CSF flow patterns with varying pulse amplitude, pulsation rate, and bulk flow rate with high throughput capabilities. These variables were specified in a custom-built user interface to match clinical CSF flow measurements. In addition to flow simulation capabilities, AIMS was developed as a modular setup for chamber testing and quality control. In this study, the capacity and consistency of single inlet resin chambers (N = 40), multidirectional resin chambers (N = 5), silicone chambers (N = 40), and PETG chambers (N = 50) were investigated. The impact of the internal geometry of the chamber types on flow vectors during pulsatile physiologic and pathophysiologic flow was visualized using Computational Fluid Dynamics (CFD). Dynamic changes in ventricular volume were investigated by combining AIMS with MRI-driven silicone model of a pediatric","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"103"},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863804","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":"Isolation method of brain microvessels from small frozen human brain tissue for blood-brain barrier protein expression analysis.","authors":"Seiryo Ogata, Shingo Ito, Takeshi Masuda, Sumio Ohtsuki","doi":"10.1186/s12987-024-00609-6","DOIUrl":"10.1186/s12987-024-00609-6","url":null,"abstract":"<p><strong>Background: </strong>Protein expression analysis of isolated brain microvessels provides valuable insights into the function of the blood-brain barrier (BBB). However, isolation of brain microvessels from human brain tissue, particularly in small quantities, poses significant challenges. This study presents a method for isolating brain microvessels from a small amount of frozen human brain tissue, adapting techniques from an established mouse brain capillary isolation method.</p><p><strong>Methods: </strong>Brain microvessel fractions were obtained from approximately 0.3 g of frozen human brain tissue (frontal cortex) using a bead homogenizer for homogenization, followed by purification with a combination of cell strainers and glass beads. Protein expression in the isolated human microvessel fractions and whole-brain lysates was analyzed by western blot and proteomic analysis.</p><p><strong>Results: </strong>Microscopic imaging confirmed the successful isolation of brain microvessels from frozen human brain tissue. Protein quantification assays demonstrated that the microvessel fraction yielded sufficient protein for detailed expression analysis. Western blot analysis revealed an enrichment of BBB-selective proteins including multidrug resistance 1 (MDR1)/ATP-binding cassette sub-family B member 1 (ABCB1), glucose transporter protein type 1 (GLUT1)/solute carrier family 2 member 1 (SLC2A1), and claudin 5 (CLDN5), in the brain microvessel fraction compared to whole-brain lysates. Multiple reaction monitoring quantification of six BBB-selective proteins-MDR1, breast cancer resistance protein (BCRP)/ATP binding cassette subfamily G member 2 (ABCG2), GLUT1, monocarboxylate transporter 1 (MCT1)/solute carrier family 16 member 1 (SLC16A1), transferrin receptor, and CLDN5-revealed expression levels consistent with those observed in larger human brain samples. Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomics further demonstrated significant enrichment of human microvascular endothelial cells in the isolated fraction, corroborating the findings from mouse models.</p><p><strong>Conclusions: </strong>We successfully developed a method for isolation of brain microvessels from a small amount of frozen human brain tissue, facilitating detailed study of BBB proteome in aging or pathological conditions. This technique provides valuable insights into BBB dysfunction in central nervous system disorders and holds potential for improving brain-targeted drug delivery strategies.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"106"},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863699","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":"Lumped parameter simulations of cervical lymphatic vessels: dynamics of murine cerebrospinal fluid efflux from the skull.","authors":"Daehyun Kim, Jeffrey Tithof","doi":"10.1186/s12987-024-00605-w","DOIUrl":"10.1186/s12987-024-00605-w","url":null,"abstract":"<p><strong>Background: </strong>Growing evidence suggests that for rodents, a substantial fraction of cerebrospinal fluid (CSF) drains by crossing the cribriform plate into the nasopharyngeal lymphatics, eventually reaching the cervical lymphatic vessels (CLVs). Disruption of this drainage pathway is associated with various neurological disorders.</p><p><strong>Methods: </strong>We employ a lumped parameter method to numerically model CSF drainage across the cribriform plate to CLVs. Our model uses intracranial pressure as an inlet pressure and central venous blood pressure as an outlet pressure. The model incorporates initial lymphatic vessels (modeling those in the nasal region) that absorb the CSF and collecting lymphatic vessels (modeling CLVs) to transport the CSF against an adverse pressure gradient. To determine unknown parameters such as wall stiffness and valve properties, we utilize a Monte Carlo approach and validate our simulation against recent in vivo experimental measurements.</p><p><strong>Results: </strong>Our parameter analysis reveals the physical characteristics of CLVs. Our results suggest that the stiffness of the vessel wall and the closing state of the valve are crucial for maintaining the vessel size and volume flow rate observed in vivo. We find that a decreased contraction amplitude and frequency leads to a reduction in volume flow rate, and we test the effects of varying the different pressures acting on the CLVs. Finally, we provide evidence that branching of initial lymphatic vessels may deviate from Murray's law to reduce sensitivity to elevated intracranial pressure.</p><p><strong>Conclusions: </strong>This is the first numerical study of CSF drainage through CLVs. Our comprehensive parameter analysis offers guidance for future numerical modeling of CLVs. This study also provides a foundation for understanding physiology of CSF drainage, helping guide future experimental studies aimed at identifying causal mechanisms of reduction in CLV transport and potential therapeutic approaches to enhance flow.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"104"},"PeriodicalIF":5.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863800","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}