Fluids and Barriers of the CNS最新文献

{"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}

{"title":"Association between choroid plexus volume and cognitive function in community-dwelling older adults without dementia: a population-based cross-sectional analysis.","authors":"Yosuke Hidaka, Mamoru Hashimoto, Takashi Suehiro, Ryuji Fukuhara, Tomohisa Ishikawa, Naoko Tsunoda, Asuka Koyama, Kazuki Honda, Yusuke Miyagawa, Kazuhiro Yoshiura, Seiji Yuuki, Naoto Kajitani, Shuken Boku, Kazunari Ishii, Manabu Ikeda, Minoru Takebayashi","doi":"10.1186/s12987-024-00601-0","DOIUrl":"10.1186/s12987-024-00601-0","url":null,"abstract":"<p><strong>Background: </strong>An increase in choroid plexus (CP) volume may be associated with cognitive decline in older individuals without dementia. In this study, we aimed to clarify whether CP volume can serve as an imaging marker of cognitive decline, determine how strongly CP volume is associated with cognitive decline, and explore factors associated with CP volume in older adults.</p><p><strong>Methods: </strong>We measured CP volume, brain parenchyma, and cerebrospinal fluid (CSF) spaces associated with disproportionately enlarged subarachnoid space hydrocephalus (DESH), an imaging feature of normal-pressure hydrocephalus, in community-dwelling older adults aged ≥ 65 years without dementia.</p><p><strong>Results: </strong>In 1,370 participants, lower Mini-Mental State Examination (MMSE) scores were significantly associated with higher CP volume, even after adjusting for DESH-related CSF space and brain parenchymal volume. CP volume was more strongly associated with MMSE scores than DESH-related CSF space and brain parenchymal volume. History of smoking, white matter hyperintensity, enlarged perivascular spaces, age, body mass index, and diabetes mellitus were also associated with increased CP volume.</p><p><strong>Conclusions: </strong>CP volume may be a highly sensitive imaging marker of cognitive decline in community-dwelling older adults without dementia, as it is linked to cognitive decline independently of brain parenchyma and CSF volumes. Our findings emphasize the importance of investigating CP volume increase to maintain cognitive function in older individuals. Accordingly, further longitudinal studies are required.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"101"},"PeriodicalIF":5.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853346","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":"Numerical study of the effects of minor structures and mean velocity fields in the cerebrospinal fluid flow.","authors":"Ziyu Wang, Mohammad Majidi, Chenji Li, Arezoo Ardekani","doi":"10.1186/s12987-024-00604-x","DOIUrl":"10.1186/s12987-024-00604-x","url":null,"abstract":"<p><p>The importance of optimizing intrathecal drug delivery is highlighted by its potential to improve patient health outcomes. Findings from previous computational studies, based on an individual or a small group, may not be applicable to the wider population due to substantial geometric variability. Our study aims to circumvent this problem by evaluating an individual's cycle-averaged Lagrangian velocity field based on the geometry of their spinal subarachnoid space. It has been shown by Lawrence et al. (J Fluid Mech 861:679-720, 2019) that dominant physical mechanisms, such as steady streaming and Stokes drift, are key to facilitating mass transport within the spinal canal. In this study, we computationally modeled pulsatile cerebrospinal fluid flow fields and Lagrangian velocity field within the spinal subarachnoid space. Our findings highlight the essential role of minor structures, such as nerve roots, denticulate ligaments, and the wavy arachnoid membrane, in modulating flow and transport dynamics within the spinal subarachnoid space. We found that these structures can enhance fluid transport. We also emphasized the need for particle tracking in computational studies of mass transport within the spinal subarachnoid space. Our research illuminates the relationship between the geometry of the spinal canal and transport dynamics, characterized by a large upward cycle-averaged Lagrangian velocity zone in the wider region of the geometry, as opposed to a downward zone in the narrower region and areas close to the wall. This highlights the potential for optimizing intrathecal injection protocols by harnessing natural flow dynamics within the spinal canal.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"102"},"PeriodicalIF":5.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853451","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":"Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.","authors":"Quentin R Smith, Haritha Mandula, Jagan Mohan R Parepally, Jun Oki, Fancy Thomas, Helen R Thorsheim, Abraham J Al-Ahmad, Thomas J Abbruscato, Per Ask, David S Hage, Peter J Robinson","doi":"10.1186/s12987-024-00584-y","DOIUrl":"10.1186/s12987-024-00584-y","url":null,"abstract":"<p><strong>Background: </strong>Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.</p><p><strong>Methods: </strong>Rat brain was perfused with physiological saline at increased flow rate and in the presence of various concentrations of plasma protein, serum albumin or alpha-acid glycoprotein. Plasma protein was added to the saline perfusion fluid to lower extraction into the measurable range using the Crone Renkin \"diffusion-flow\" equation to calculate brain P_oS.</p><p><strong>Results: </strong>Cerebrovascular P_o was determined for 125 solutes, of which 78 showed little or no evidence of active efflux transport. Fifty of the solutes were in the lipophilicity zone (Log P_oct 1-5) of most FDA-approved CNS drugs. Care was taken to ensure the integrity of the brain vasculature during perfusion and to measure flow accurately using markers that had been verified for the flow rates. The results showed a linear relationship between Log P_o and Log P_oct over ~10 orders of magnitude with values for diazepam, estradiol, testosterone, and other agents that exceed prior published values by fivefold to 200-fold.</p><p><strong>Conclusions: </strong>The results show that brain vascular permeability can be measured directly in vivo for highly lipophilic solutes and the PS values obtained match reasonably with that predicted by the Crone-Renkin flow diffusion equation with care taken to validate the accuracy for the component measurements and with no need to invoke \"enhanced\" or \"induced\" dissociation.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"100"},"PeriodicalIF":5.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846244","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":"Abstracts from Hydrocephalus 2024: The 16th Meeting of the Hydrocephalus Society.","authors":"","doi":"10.1186/s12987-024-00596-8","DOIUrl":"10.1186/s12987-024-00596-8","url":null,"abstract":"","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 Suppl 1","pages":"99"},"PeriodicalIF":5.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812654","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}