Fluids and Barriers of the CNS最新文献

{"title":"PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier.","authors":"Anikó Szecskó, Mária Mészáros, Beatriz Simões, Marco Cavaco, Catarina Chaparro, Gergő Porkoláb, Miguel A R B Castanho, Mária A Deli, Vera Neves, Szilvia Veszelka","doi":"10.1186/s12987-025-00641-0","DOIUrl":"10.1186/s12987-025-00641-0","url":null,"abstract":"<p><strong>Background: </strong>Nanocarriers targeting the blood-brain barrier (BBB) are promising drug delivery systems to enhance the penetration of therapeutic molecules into the brain. Immunotherapy, particularly monoclonal antibodies designed to bind amyloid-beta peptides have become a promising strategy for Alzheimer's disease, but ensuring efficacy and safety is challenging and crucial for these therapies. Our aim was to develop an innovative nanocarriers conjugated with PepH3, a cationic peptide derived from Dengue virus type-2 capsid protein that crosses the BBB and acts as a shuttle peptide for the encapsulated single domain antibody (sdAb) recognizing Aβ oligomers.</p><p><strong>Results: </strong>PepH3 peptide enhanced the uptake of the nanoparticles (NPs) into brain endothelial cells, and transcytosis of sdAb, as a potential therapeutic molecule, across both rat and human BBB culture models. The cargo uptake was a temperature dependent active process that was reduced by metabolic and endocytosis inhibitors. The cellular uptake of the cationic PepH3-tagged NPs decreased when the negative surface charge of brain endothelial cells became more positive after treatments with a cationic lipid or with neuraminidase by digesting the glycocalyx. The NPs colocalized mostly with endoplasmic reticulum and Golgi apparatus and not with lysosomes, indicating the cargo may avoid cellular degradation.</p><p><strong>Conclusions: </strong>Our results support that combination of NPs with a potential brain shuttle peptide such as PepH3 peptide can improve the delivery of antibody fragments across the BBB.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"31"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763409","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 cells as phagocytes: mechanisms and implications.","authors":"Rudy T Chang, Mark J Fisher, Rachita K Sumbria","doi":"10.1186/s12987-025-00637-w","DOIUrl":"10.1186/s12987-025-00637-w","url":null,"abstract":"<p><p>Brain microvascular endothelial cells (BECs) lining the brain capillaries form the anatomical site of the blood-brain barrier (BBB), providing a highly selective barrier to support brain homeostasis and function. While the BBB acts as a barrier to immune cells and pathogens under normal conditions, BECs can facilitate their entry into the CNS via a phagocytosis-like mechanism. A similar process is now increasingly reported for a diverse set of cargos, resulting in the categorization of BECs as \"non-professional\" phagocytes and redefining the conventional view that these cells are functionally non-phagocytic. This review aims to summarize research demonstrating the capacity of BECs to phagocytose various cargos, including aged red blood cells (RBC), myelin debris, and embolic particles. Mechanistically, BEC phagocytosis can be triggered by the exposure of phosphatidylserine on RBC, expression of adhesion molecules such as ICAM-1 and VCAM-1 on BECs, cargo-opsonization, and/or involve BEC cytoskeleton remodeling. Phagocytic activity by BECs has significant clinical implications ranging from regulation of cerebral microvascular patency (particularly by contributing to and resolving capillary stalling), clearance of brain parenchymal debris, and brain parenchymal invasion by pathogens. Further, BEC phagocytosis of RBC, which represents a cell (RBC)-in-cell (BEC) phenomenon, is implicated in hemorrhagic lesions including cerebral microhemorrhages. This review aims to shed light on BEC phagocytosis as an important function within the brain microvascular system and will delve into the underlying mechanisms, discuss the clinical implications, and identify gaps in our understanding of this phenomenon.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"30"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763257","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":"Is the ischemia found in normal pressure hydrocephalus secondary to venous compression or arterial constriction? A comment on Ohmura et al.","authors":"Grant Alexander Bateman, Alexander Robert Bateman","doi":"10.1186/s12987-025-00640-1","DOIUrl":"10.1186/s12987-025-00640-1","url":null,"abstract":"<p><strong>Background: </strong>In a recent study of normal pressure hydrocephalus published by Ohmura et al., there was a progressive reduction in the cerebral blood volume within the cortex, as measured by near-infrared spectroscopy, following an increase in the intracranial pressure from an infusion study. The authors contend that this reduction in blood volume occurred due to the collapse of the venous structures, starting from the smallest veins adjacent to the capillaries and involving the entire venous outflow tract. We wish to outline some problems with this interpretation.</p><p><strong>Main body: </strong>It has been previously shown that venous collapse secondary to an increase in intracranial pressure always starts at the most distal point in the veins. The critical buckling pressure for a tube depends on the cube of the ratio of the wall thickness and the internal diameter. The smallest veins have ratios which are larger than the distal cortical veins, so the latter are the ones to collapse first. The collapse of the distal venous outflow cuff always leads to an increase in the transmural pressure of the veins upstream from it, leading to venous dilatation and not a reduction in venous volume. Only a simultaneous arteriolar constriction of a greater volume than the venous volume increase can account for the progressive reduction in blood volume, which occurs once the ICP is greater than the sinus outflow pressure in normal pressure hydrocephalus.</p><p><strong>Conclusions: </strong>The reduction in cerebral blood volume which occurs in the cortex in normal pressure hydrocephalus cannot be due to widespread venous collapse. Therefore, there must be a large component of arteriolar constriction accompanying this disease.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"29"},"PeriodicalIF":5.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662734","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":"VIEshunt: towards a ventricular intelligent and electromechanical shunt for hydrocephalus therapy.","authors":"Fabian Flürenbrock, Leonie Korn, Dominik Schulte, Anthony Podgoršak, Joris Chomarat, Janina Hug, Tiago Hungerland, Caroline Holzer, David Iselin, Luca Krebs, Rosina Weiss, Markus F Oertel, Lennart Stieglitz, Miriam Weisskopf, Mirko Meboldt, Melanie N Zeilinger, Marianne Schmid Daners","doi":"10.1186/s12987-025-00629-w","DOIUrl":"10.1186/s12987-025-00629-w","url":null,"abstract":"<p><strong>Background: </strong>Shunt systems for hydrocephalus therapy are commonly based on passive mechanical pressure valves that are driven by the intracranial, intra-abdominal, and hydrostatic pressure. The differential pressure acting on the valve determines the drainage rate of cerebrospinal fluid (CSF) but is not a gauge of the physiological condition of the patient. Internal and external influences can cause over- or underdrainage and lead to pathological levels of intracranial pressure (ICP).</p><p><strong>Methods: </strong>The first prototype of a ventricular intelligent and electromechanical shunt (VIEshunt) is developed, tested, and compared with previous efforts towards the development of a smart shunt. Its key components are a micro pump, a flow meter, a pressure sensor, an inertial measurement unit, a wireless communication interface, and a microcontroller. The VIEshunt prototype was tested in vitro using a hardware-in-the-loop (HiL) test bench that runs real-time patient simulations involving changes in intracranial and intra-abdominal pressure, as well as changes in posture ranging between supine and upright position. The prototype was subsequently tested in an in vivo pilot study based on an acute ovine animal model (n=1) with infusions of artificial CSF.</p><p><strong>Results: </strong>During 24 h in vitro testing, the prototype detected the simulated posture changes of the patient and automatically adapted the controller reference. The posture-specific ICP references of 12 mmHg for supine and -3 mmHg for upright position were tracked without offset, thus preventing adverse over- and underdrainage during the investigated HiL test scenario. During acute in vivo testing, the prototype first regulated the mean ICP of a sheep from 22 mmHg down to 20 mmHg. Each of the three subsequent intraventricular bolus infusions of 1 mL saline solution increased mean ICP by approximately 11 mmHg. While natural absorption alone decreased ICP by only 5 mmHg within 9 min, the prototype was able to regulate ICP back to the pre-bolus pressure value within 5 min.</p><p><strong>Conclusion: </strong>The developed VIEshunt prototype is capable of posture-dependent ICP regulation and CSF drainage control. Smart shunt systems based on VIEshunt could improve patient monitoring and enable optimal physiologic therapy by adapting to the individual patient. To derive statistically relevant conclusions for the performance of VIEshunt, future work will focus on the development of a next generation prototype for use in pre-clinical studies.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"28"},"PeriodicalIF":5.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633809","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":"Hypoxemia exerts detrimental effects on the choroid plexuses and cerebrospinal fluid system in rats.","authors":"Rawan Barakat, Hameed Al-Sarraf, Zoran Redzic","doi":"10.1186/s12987-024-00613-w","DOIUrl":"10.1186/s12987-024-00613-w","url":null,"abstract":"<p><strong>Background: </strong>Hypoxemia can cause secondary acute brain injury, but the mechanisms behind it are not entirely clear and could involve disturbances in the brain extracellular fluids. We aimed to explore the effects of hypoxemia on the choroid plexus (CPs) and cerebrospinal fluid (CSF) system in rats.</p><p><strong>Methods: </strong>Male Sprague Dawley rats were kept in O₂ control in vivo cabinet with either 21% (normoxia) or 8% O₂ (hypoxemia) for up to 48 h. In some cases, signaling of selected cytokines was inhibited prior to hypoxemia. CSF and blood samples were collected by Cisterna Magna puncture and through venous catheters, respectively. The percentages of dead cells in the CPs and ependymal layers (EL) after hypoxemia or normoxia was estimated using TUNEL staining. CP's ultrastructure was analyzed by transmission electron microscopy. Protein concentration in the CSF and plasma was measured and the CSF albumin-to-total protein ratios were estimated. Concentrations of hypoxia-related cytokines in the CSF and plasma samples were estimated using the multiplex immunoassay. Data was analyzed by one-way ANOVA followed by either Bonferroni or Tukey's multiple comparison tests, or Student's t-test. Results are presented as mean ± SD; p < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Duration of hypoxemia exerted significant effects on the cell viability in the CPs (p < 0.01) and EL (p < 0.01) and caused apoptosis-related changes in the CP. Hypoxemia had significant effects on the protein concentration in the CSF (p < 0.05), but not in plasma (p > 0.05), with a significant increase in the CSF albumin-to-total protein ratio after 6 h hypoxemia (p < 0.05). Thirty-two cytokines were detected in the CSF. Hypoxemia caused a statistically significant reduction in the concentrations of 12 cytokines, while concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increased significantly. Exposure to hypoxemia after inhibitions of EPO, VEGF, or tumor necrosis factor alpha (TNFα) signaling resulted in more dead cells (p < 0.01), less dead cells (p < 0.01) and more dead cells (p < 0.01) in the CPs, respectively, when compared to the number of dead cells when these cytokines were not inhibited. The density of macrophages in the CPs decreased significantly during hypoxemia; that effect was cancelled out by TNFα inhibition.</p><p><strong>Conclusion: </strong>Hypoxemia had detrimental effects on the CPs and CSF system, which was modulated by hypoxia- and inflammation-related cytokines.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"27"},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614108","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":"Ventriculosagittal sinus shunt for treating hydrocephalus with elevated cerebrospinal fluid protein.","authors":"Yikang Wang, Di Wang, Yu Tian, Yilong Yao, Qi Yu","doi":"10.1186/s12987-025-00633-0","DOIUrl":"10.1186/s12987-025-00633-0","url":null,"abstract":"<p><p>This study aimed to investigate the feasibility, acceptability, and preliminary efficacy of a ventriculosagittal sinus (VSS) shunt in the treatment of hydrocephalus with elevated cerebrospinal fluid (CSF) protein content. In this single-center retrospective analysis, we enrolled 80 patients with hydrocephalus and elevated CSF protein levels. Based on these procedures, primary cohort was divided into two groups using CSF protein (CSFP) for subsequent analysis to determine the relationship between the clinical effect and CSFP. Preoperative and postoperative computer tomography (CT) scans, clinical symptoms, and CSF laboratory test were compared. Clinical records of 80 patients were analyzed; 44 patients received VSS shunt, 30 patients received ventriculoperitoneal (VP) shunt, and 6 patients received ventriculobladder (VB) shunt. The most significant changes in ventricular size in the VSS shunt group were detected on the 7th day postoperatively from the collected imaging data. Six months after shunt surgery, the overall success rate for VSS shunt (35 of 44, 79.5%) was markedly higher than that for VP shunt (12 of 30, 40%) and VB shunt (1 of 6, 16.7%). The VSS shunt has a positive clinical effect in hydrocephalus with abnormal CSF laboratory results (elevated protein levels), which is more significant than the clinical success rate of VP shunt in terms of both symptoms and imaging results. The degree of relief and improvement of imaging and symptoms were unrelated to the CSFP content. There was no significant difference in the efficacy of VSS shunt between the CSFP < 1.0 g/L group and the CSFP > 1.0 g/L group. No intracranial or extracranial complications related to the surgery were noted during follow-up. The VSS shunt should be considered the first-line treatment option in cases of hydrocephalus with elevated CSFP levels. Moreover, VSS shunt can immediately improve symptoms and alleviate hydrocephalus even though the CSFP was elevated.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"26"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604127","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":"A review of cerebrospinal fluid circulation with respect to Chiari-like malformation and syringomyelia in brachycephalic dogs.","authors":"Ryan Jones, Srdjan Cirovic, Clare Rusbridge","doi":"10.1186/s12987-025-00636-x","DOIUrl":"10.1186/s12987-025-00636-x","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) plays a crucial role in maintaining brain homeostasis by facilitating the clearance of metabolic waste and regulating intracranial pressure. Dysregulation of CSF flow can lead to conditions like syringomyelia, and hydrocephalus. This review details the anatomy of CSF flow, examining its contribution to waste clearance within the brain and spinal cord. The review integrates data from human, canine, and other mammalian studies, with a particular focus on brachycephalic dogs. Certain dog breeds exhibit a high prevalence of CSF-related conditions due to artificial selection for neotenous traits, making them valuable models for studying analogous human conditions, such as Chiari-like malformation and syringomyelia associated with craniosynostosis. This review discusses the anatomical features specific to some brachycephalic breeds and the impact of skull and cranial cervical conformation on CSF flow patterns, providing insights into the pathophysiology and potential modelling approaches for these conditions.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"25"},"PeriodicalIF":5.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596624","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 non-invasive therapies to improve hydrocephalus outcomes.","authors":"Alexandra Hochstetler, Christine Hehnly, William Dawes, Daniel Harris, Cameron Sadegh, Francesco T Mangano, Samantha N Lanjewar, Monica J Chau","doi":"10.1186/s12987-025-00632-1","DOIUrl":"10.1186/s12987-025-00632-1","url":null,"abstract":"<p><p>The Hydrocephalus Association organized two workshops with the support of the Rudi Schulte Research Institute and Cincinnati Children's Hospital Medical Center entitled \"Developing Non-Invasive Hydrocephalus Therapies: Molecular and Cellular Targets\", held September 27-29, 2023, in Dallas, TX, and \"Developing Non-Invasive Hydrocephalus Therapies: Advancing Towards Clinical Trials\", held April 12-13, 2024, in Cincinnati, OH. The goal of these workshops was to explore the frontiers of ongoing research for non-invasive therapies for the treatment of hydrocephalus across all etiologies and to improve patient outcomes at all stages of diagnosis and management. During the consensus-building discussions throughout the research workshops, basic, translational, and clinical scientists aimed to identify the next steps to develop novel treatments for hydrocephalus. This detailed report discusses the research priorities that emerged from these workshops to inspire researchers and guide studies towards better treatment for people living with hydrocephalus.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"24"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540690","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":"Applying machine learning to high-dimensional proteomics datasets for the identification of Alzheimer's disease biomarkers.","authors":"Christoffer Ivarsson Orrelid, Oscar Rosberg, Sophia Weiner, Fredrik D Johansson, Johan Gobom, Henrik Zetterberg, Newton Mwai, Lena Stempfle","doi":"10.1186/s12987-025-00634-z","DOIUrl":"10.1186/s12987-025-00634-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study explores the application of machine learning to high-dimensional proteomics datasets for identifying Alzheimer's disease (AD) biomarkers. AD, a neurodegenerative disorder affecting millions worldwide, necessitates early and accurate diagnosis for effective management.</p><p><strong>Methods: </strong>We leverage Tandem Mass Tag (TMT) proteomics data from the cerebrospinal fluid (CSF) samples from the frontal cortex of patients with idiopathic normal pressure hydrocephalus (iNPH), a condition often comorbid with AD, with rare access to both lumbar and ventricular samples. Our methodology includes extensive data preprocessing to address batch effects and missing values, followed by the use of the Synthetic Minority Over-sampling Technique (SMOTE) for data augmentation to overcome the small sample size. We apply linear, and non-linear machine learning models, and ensemble methods, to compare iNPH patients with and without biomarker evidence of AD pathology ( <math><mrow><mi>A</mi> <msup><mi>β</mi> <mo>-</mo></msup> <msup><mi>T</mi> <mo>-</mo></msup> </mrow> </math> or <math><mrow><mi>A</mi> <msup><mi>β</mi> <mo>+</mo></msup> <msup><mi>T</mi> <mo>+</mo></msup> </mrow> </math> ) in a classification task.</p><p><strong>Results: </strong>We present a machine learning workflow for working with high-dimensional TMT proteomics data that addresses their inherent data characteristics. Our results demonstrate that batch effect correction has no or minor impact on the models' performance and robust feature selection is critical for model stability and performance, especially in the high-dimensional proteomics data setting for AD diagnostics. The results further indicated that removing features with missing values produced stronger models than imputing them, and the batch effect had minimal impact on the models Our best-performing disease-progression detection model, a random forest, achieves an AUC of 0.84 (± 0.03).</p><p><strong>Conclusion: </strong>We identify several novel protein biomarkers candidates, such as FABP3 and GOT1, with potential diagnostic value for AD pathology detection, suggesting the necessity of different biomarkers for AD diagnoses for patients with iNPH, and considering different biomarkers for ventricular and lumbar CSF samples. This work underscores the importance of a meticulous machine learning process in enhancing biomarker discovery. Our study also provides insights in translating biomarkers from other central nervous system diseases like iNPH, and both ventricular and lumbar CSF samples for biomarker discovery, providing a foundation for future research and clinical applications.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"23"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540678","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":"Hippocampal vascularization pattern and cerebral blood flow cooperatively modulate hippocampal tolerable amount of Aβ deposition in the occurrence of MCI.","authors":"Yuhao Xu, Hong Wei, Rui Du, Ranchao Wang, Yan Zhu, Tian Zhao, Xiaolan Zhu, Yuefeng Li","doi":"10.1186/s12987-025-00635-y","DOIUrl":"10.1186/s12987-025-00635-y","url":null,"abstract":"<p><strong>Background: </strong>Aβ deposition in the brain does not necessarily lead to cognitive impairment, and that blood supply may have other unexplained regulatory effects on Aβ. Therefore, there appears to be a more complex relationship between blood supply, Aβ deposition, and cognitive impairment that warrants further exploration.</p><p><strong>Methods: </strong>This cohort study collected four longitudinal follow-up datasets, including a total of 281 subjects, followed for four years. Three-dimensional time-of-flight angiography and pseudo-continuous arterial spin labeling were used to assess hippocampal vascularization pattern (VP) and hippocampal cerebral blood flow (CBF). 11 C-Pittsburgh compound B (PiB)-PET/CT-based spatial measurements were used detect hippocampal PiB uptake as a reflection of hippocampal Aβ deposition. We explored the relationships between hippocampal blood supply (VP and CBF), hippocampal PiB uptake, and the occurrence of mild cognitive impairment (MCI) using a generalized nonlinear model.</p><p><strong>Results: </strong>We demonstrated the synergistic effect of hippocampal VP and CBF on predicting the occurrence of MCI. We conducted confirmation and quantification of the relationship between hippocampal blood supply and hippocampal PiB uptake. Additionally, the predicted value of PiB uptake based on hippocampal blood supply not only exhibited strong predictive efficacy for the occurrence of MCI (AUC = 0.831, p < 0.001), but was also validated in cerebral small vessel disease cohorts (AUC = 0.792, p < 0.001) and well validated in an independent cohort (Kappa = 0.741, p < 0.001).</p><p><strong>Conclusions: </strong>Overall, we reveal that hippocampal blood supply at baseline can regulate hippocampal PiB uptake, which reflects hippocampal tolerable amount of Aβ deposition and serves as an effective predictor for the occurrence of MCI, providing an important extension on the relationship between hippocampal blood supply and Aβ deposition.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"22"},"PeriodicalIF":5.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491458","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}