Fluids and Barriers of the CNS最新文献

{"title":"Choroid plexus enlargement correlates with subcortical tau deposition in progressive supranuclear palsy.","authors":"Na Wang, JiaYing Lu, XueLing Liu, JianPeng Liu, YuCheng Lu, ChengLing Xu, SiRong Piao, LiQin Yang, FengTao Liu, YuXin Li","doi":"10.1186/s12987-025-00663-8","DOIUrl":"10.1186/s12987-025-00663-8","url":null,"abstract":"<p><strong>Objective: </strong>The choroid plexus (CP) has gained renewed attention for its role in waste clearance in neurodegenerative disorders. However, its involvement in progressive supranuclear palsy (PSP) remains unclear. This study aimed to investigate CP volume changes in patients with PSP compared to Parkinson's disease (PD), and explore its relationship with tau deposition in PSP patients.</p><p><strong>Methods: </strong>A total of 204 participants (92 PSP, 78 PD, 34 healthy controls (HC)) underwent structural MRI, with 63 PSP patients receiving ¹⁸F-Florzolotau positron emission tomography. CP volume was compared across the three groups, and its ability to differentiate PSP from PD was assessed. Mean standardized uptake value ratios (SUVRs) from bilateral subcortical regions were extracted: ROIs1 including early involved nuclei of red nucleus, subthalamic nucleus, raphe nuclei, and globus pallidus; ROIs2 including late involved nuclei of substantia nigra, locus coeruleus, putamen, and thalamus. The relationship between CP volume, tau deposition and clinical assessments was analyzed.</p><p><strong>Results: </strong>PSP patients exhibited increased CP volume compared to PD and HC groups. The area under the curve value was 0.84 in differentiating PSP from PD, with CP volume and age as predictive variables. In the PSP group, CP volume was positively correlated with mean ¹⁸F-Florzolotau SUVRs in the ROIs2. Furthermore, in the PSP and PD groups, CP volume was negatively correlated with cognitive scores, but positively correlated with motor scores.</p><p><strong>Conclusions: </strong>CP enlargement is a distinguishing feature of PSP and may serve as an imaging biomarker for tau accumulation, offering potential for differentiating PSP from PD.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"52"},"PeriodicalIF":5.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141777","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":"Idiopathic normal pressure hydrocephalus: associations between CSF biomarkers, clinical symptoms, and outcome after shunt surgery.","authors":"Majd Saadaldeen, Anna Jeppsson, Per Hellström, Kaj Blennow, Henrik Zetterberg, Carsten Wikkelsø, Mats Tullberg","doi":"10.1186/s12987-025-00661-w","DOIUrl":"10.1186/s12987-025-00661-w","url":null,"abstract":"<p><strong>Background: </strong>The neurochemical alterations in cerebrospinal fluid (CSF) associated with the typical symptomatology in idiopathic normal pressure hydrocephalus (iNPH) and their association with outcome after shunt surgery are unsettled.</p><p><strong>Aim: </strong>To explore associations between concentrations of CSF biomarkers reflecting amyloid- and tau pathology, neuronal degeneration as well as astrocytic activation and the characteristic symptomatology in iNPH and to examine whether these biomarkers can predict the postoperative outcome in all patients and in patients without evidence of Alzheimer's disease (AD) pathology.</p><p><strong>Methods: </strong>This explorative study included 81 patients diagnosed with iNPH at the Hydrocephalus research unit, Sahlgrenska. Symptoms were assessed using the iNPH-scale and standardized clinical tests measuring gait, balance, cognition and urinary incontinence before and median 8 months after shunt surgery. Pre-operative lumbar CSF concentrations of Aβ38, Aβ40, Aβ42, ratio Aβ42/Aβ40, sAPPα, sAPPβ, T-tau, P-tau, MCP-1, and NFL were analyzed. A low Aβ42/Aβ40 ratio defined patients with AD pathology. Correlation and regression analyses between biomarker concentrations and clinical symptoms at baseline as well as postoperative change in symptoms after surgery, were performed.</p><p><strong>Results: </strong>Higher NFL correlated with more pronounced impairment in all clinical tests, i.e. included measures of gait, balance, cognition and urinary incontinence (r_p=0.25-0.46, p < 0.05). Higher T-tau and P-tau correlated with poorer performance in cognitive tests (r_p=0.26-0.39, p < 0.05). No biomarker could differentiate between improved and unimproved patients in the whole sample or in AD-pathology negative patients. Low ratio Aβ42/Aβ40 lacked predictive value. A higher preoperative P-tau was weakly correlated with less pronounced overall clinical improvement (r_p = -0.238, p = 0.036).</p><p><strong>Conclusions: </strong>Axonal degeneration, as indicated by elevated NFL, is probably involved in the generation of the full iNPH tetrade of symptoms and tau pathology more specifically with iNPH cognitive impairment. No CSF biomarker could identify shunt responders. CSF evidence of Alzheimer pathology should not be used to exclude patients from shunt surgery.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"51"},"PeriodicalIF":5.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101633","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":"Review of the lumbar infusion test use in pediatric populations: state-of-the-art and future perspectives.","authors":"Vojtěch Novák, Adéla Bubeníková, Petr Skalický, Arnošt Mládek, Václav Gerla, Afroditi Despina Lalou, Aleš Vlasák, Róbert Leško, Ondřej Bradáč","doi":"10.1186/s12987-025-00662-9","DOIUrl":"10.1186/s12987-025-00662-9","url":null,"abstract":"<p><strong>Background: </strong>The lumbar infusion test (LIT) is a routine part of the diagnostic process of various CSF dynamics disorders in adults. However, it is rarely used in the paediatric population due to a lack of evidence substantiating its efficacy and overall indications.</p><p><strong>Methods: </strong>Articles utilizing the LIT in a paediatric cohort (≤ 18 years) were included according to the PRISMA guidelines with the Newcastle-Ottawa Scale to assess the risk of bias. This review was registered at PROSPERO database under number: CRD42024625857.</p><p><strong>Results: </strong>A total of 15 studies, yielding 441 patients, were included in the review. The most common indications for LIT were to predict shunt responsiveness in hydrocephalus and idiopathic intracranial hypertension (IIH). In IIH, the interaction between cerebrospinal fluid pressure (CSFp) and sagittal sinus pressure (SSp) may offer valuable diagnostic insights and present a novel assessment approach. The LIT is a validated tool, especially effective for predicting shunt responsiveness and detecting malfunctions in both IIH and hydrocephalus.</p><p><strong>Conclusions: </strong>Data surrounding LIT usage in children is lacking and most studies are outdated. Caution is needed when interpreting resistance to outflow (Rout) due to potential overestimation, with more attention directed to CSFp and the pressure within the venous system coupling in IIH. Future studies should focus on standardizing LIT protocols across age groups with focusing more on signal characteristics rather than individual parameters and fostering interdisciplinary collaboration to optimize diagnostic accuracy.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"50"},"PeriodicalIF":5.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076760","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":"BBB proteomic analysis reveals that complex febrile seizures in infancy enhance susceptibility to epilepsy in adulthood through dysregulation of ECM-receptor interaction signaling pathway.","authors":"Qian Wang, Liangyu Pan, Siruan Chen, Yuyu Zhang, Guangyuan Liu, Yiying Wu, Xia Qin, Panpan Zhang, Wei Zhang, Jianghua Zhang, Dezhi Kong","doi":"10.1186/s12987-025-00660-x","DOIUrl":"10.1186/s12987-025-00660-x","url":null,"abstract":"<p><strong>Background: </strong>Complex febrile seizures (CFS) have been associated with an increased risk of epilepsy in adulthood. However, the specific link between blood-brain barrier (BBB) and the predisposition to epilepsy in adults who experienced CFS during infancy remains unclear. The objective of this study was to investigate the alteration of BBB in adult mice who had experienced CFS during infancy, and to explore the mechanisms of increased susceptibility to epilepsy after CFS.</p><p><strong>Methods: </strong>The CFS pup model was induced using hot air, and the seizure susceptibility was examined using low-dose pentylenetetrazole (PTZ) after 8 W. The brain microvessels representing BBB function were isolated and their protein expression changes were analyzed using data-independent acquisition (DIA) proteomic techniques. Subsequently, the bioinformatic analyses were performed using ClusterProfiler, STRING, Gene Set Enrichment Analysis (GSEA), etc. The enriched pathways, changes in the expression of BBB-related proteins, and alterations in metabolites including certain neurotransmitters were subsequently validated by Western Blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and mass spectrometric imaging (MSI). In addition, we selected the MMP inhibitor Incyclinide to verify that dysregulation of the ECM-receptor interaction signaling pathway increases epilepsy susceptibility in adult mice.</p><p><strong>Results: </strong>Mice that experienced CFS in infancy show increased susceptibility to epilepsy in adulthood, and BBB proteomic profile was significantly altered in the CFS mice. The network analysis suggests that dysregulation of the extracellular matrix (ECM)-receptor interaction pathway is a key mechanism. Moreover, MSI analysis uncovered notable changes in differential metabolites, including amino acids and nucleotide-derived neurotransmitters associated with the function of BBB maintaining neuronal homeostasis. Subsequent validation experiments showed that dysregulation of the ECM-receptor interaction signaling pathway exacerbated epilepsy susceptibility in adult mice.</p><p><strong>Conclusion: </strong>Our research represents the pioneering demonstration of the modified BBB proteomics associated with epilepsy susceptibility in adult mice previously exposed to CFS in infancy. Notably, the increased susceptibility is attributed to the dysregulation of the ECM-receptor interaction pathway. These findings may help to elucidate the role of BBB alterations in the progression of epilepsy susceptibility, and provide new orientations for subsequent prevention and treatment of epilepsy.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"49"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981299","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 glycosaminoglycan chains of perlecan regulate the perivascular fluid transport.","authors":"Abhishek Singh, Mika Kaakinen, Harri Elamaa, Vesa Kiviniemi, Lauri Eklund","doi":"10.1186/s12987-025-00648-7","DOIUrl":"https://doi.org/10.1186/s12987-025-00648-7","url":null,"abstract":"<p><strong>Background: </strong>The perivascular conduct pathway that connects the cerebrospinal fluid spaces with the interstitial fluid in the parenchyma are of importance for solute clearance from the brain. In this pathway, the relatively wide perivascular space (PVS) surrounding the pial arteries provides a low-resistant passage while around the perforating arteries, the solute movement is along the basement membrane (BM), that prevents the free exchange of interstitial fluids and solutes. We hypothesize that this selectivity involves specific components of the vascular BM, which is mainly composed of type IV collagen (Col IV) and laminin networks interconnected by nidogens and heparan sulphate proteoglycans (HSPGs). Perlecan is the major HSPG in the BM that binds to Col IV and laminin via glycosaminoglycan (GAG) chains to form a molecular sieve. GAGs may also provide the charge selectivity required for filtration, and also a scaffold for amyloid-β (Aβ) aggregation. The purpose of this study was the functional characterization of perivascular fluid transport and brain clearance in mice lacking perlecan GAG chains.</p><p><strong>Methods: </strong>We generated a novel mouse line (Hspg2^∆3∆91) lacking perlecan GAG side chains and investigated perivascular flow and brain clearance in these mice using intravital multiphoton and fluorescence recovery after photobleaching techniques, and functional assays with various tracers. Potentially deleterious effects on brain homeostasis were investigated using transcriptomic, proteomic and immunohistochemical methods. The Hspg2^∆3∆91 mice were crossed with a 5xFAD line to examine the importance of GAGs in Aβ aggregation.</p><p><strong>Results: </strong>We observed a delayed inflow of CSF tracer into the Hspg2^∆3∆91 brain with no changes in the clearance of parenchymal injected tracers. Quantification of the Aβ plaques revealed fewer and smaller plaques in the walls of the pial arteries at six months of age, but not in the brain parenchyma. Surprisingly, perlecan GAG deficiency had no severe deleterious effects on brain homeostasis in transcriptomic and proteomic analyses.</p><p><strong>Conclusions: </strong>Potential brain clearance mechanisms are dependent on the flow through special ECM structures. BM is mainly known for its barrier function, whereas very little is known about how passage along the perivascular ECM is established. This study shows that the GAG composition of the BM affects the solute dynamics and Aβ deposition in the periarterial space.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"48"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990983","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":"Relevance of choroid plexus volumes in multiple sclerosis.","authors":"Britta Krieger, Barbara Bellenberg, Anna Katharina Roenneke, Ruth Schneider, Theodoros Ladopoulos, Zainab Abbas, Rebekka Rust, Tanja Schmitz-Hübsch, Claudia Chien, Ralf Gold, Friedemann Paul, Carsten Lukas","doi":"10.1186/s12987-025-00656-7","DOIUrl":"10.1186/s12987-025-00656-7","url":null,"abstract":"<p><strong>Background: </strong>The choroid plexus (ChP) plays a pivotal role in inflammatory processes that occur in multiple sclerosis (MS). The enlargement of the ChP in relapsing-remitting multiple sclerosis (RRMS) is considered to be an indication of disease activity and has been associated with periventricular remyelination failure. This cross-sectional study aimed to identify the relationship between ChP and periventricular tissue damage which occurs in MS, and to elucidate the role of neuroinflammation in primary progressive multiple sclerosis (PPMS).</p><p><strong>Methods: </strong>ChP volume was assessed by a novel deep learning segmentation method based on structural MRI data acquired from two centers. In total, 141 RRMS and 64 PPMS patients were included, along with 75 healthy control subjects. In addition, T1w/FLAIR ratios were calculated within periventricular bands to quantify microstructural tissue damage and to assess its relationship to ChP volume.</p><p><strong>Results: </strong>When compared to healthy controls, ChP volumes were significantly increased in RRMS, but not in patients with PPMS. T1w/FLAIR ratios in the normal appearing white matter (NAWM) showing periventricular gradients were decreased in patients with multiple sclerosis when compared to healthy control subjects and lower T1w/FLAIR ratios radiating out from the lateral ventricles were found in patients with PPMS. A relationship between ChP volume and T1w/FLAIR ratio in NAWM was found within the inner periventricular bands in RRMS patients. A longer duration of disease was associated with larger ChP volumes only in RRMS patients. Enlarged ChP volumes were also significantly associated with reduced cortex volumes and increased lesion volumes in RRMS.</p><p><strong>Conclusions: </strong>Our analysis confirmed that the ChP was significantly enlarged in patients with RRMS, which was related to brain lesion volumes and which suggested a dynamic development as it was associated with disease duration. Plexus enlargement was further associated with periventricular demyelination or tissue damage assessed by T1w/FLAIR ratios in RRMS. Furthermore, we did not find an enlargement of the ChP in patients with PPMS, possibly indicating the reduced involvement of inflammatory processes in the progressive phase of MS. The association between enlarged ChP volumes and cortical atrophy in RRMS highlighted the vulnerability of structures close to the CSF.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"47"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958727","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 legacy of William M. Pardridge (1947-2024) on the science and fields concerned with the physiology of the blood-brain barrier and the transport of drugs to the brain.","authors":"Ruben J Boado, Ulrich Bickel, Rachita K Sumbria","doi":"10.1186/s12987-025-00659-4","DOIUrl":"https://doi.org/10.1186/s12987-025-00659-4","url":null,"abstract":"<p><p>This article highlights the scientific achievements and professional career of William M. Pardridge, who passed away on 18th of June 2024. He was born in 1947 in Bethesda, Maryland, USA. William, known affectionately as Bill, was one of the most influential researchers in the blood-brain barrier (BBB) field. Bill's research contributions to the field spun over 6 decades at the University of California, Los Angeles, and it was focused on the molecular physiology of the BBB, including the carrier-mediated transport of nutrients and small molecule drugs, the receptor-mediated transport of peptides and molecular Trojan horses, gene therapy of the brain with Trojan horse liposomes, and BBB genomics and proteomics. He founded ArmaGen Inc. in 2004, a biotech company that provided the basis for the treatment of CNS disorders with the molecular Trojan horse technology. This technology continues to be widely used in academia and in the biotech industry. He has been a cherished friend and mentor to many within the BBB community.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"46"},"PeriodicalIF":5.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999215","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":"Inhibition of histone deacetylase 6 activity mitigates neurological impairment and post-hemorrhagic hydrocephalus after intraventricular hemorrhage by modulating pyroptosis and autophagy pathways.","authors":"Hao-Xiang Wang, Zi-Ang Deng, Yuan-You Li, Jun Li, Ya-Xing Chen, Yan-Jie Zhao, Ke-Ru Huang, Wei-Ning Tian, Ai-Ping Tong, Liang-Xue Zhou","doi":"10.1186/s12987-025-00658-5","DOIUrl":"https://doi.org/10.1186/s12987-025-00658-5","url":null,"abstract":"<p><strong>Background: </strong>Posthemorrhagic hydrocephalus (PHH) is a frequent and significant complication that impacts the prognosis of patients suffering from intraventricular hemorrhage (IVH). However, the underlying mechanism is uncertain. Neuronal pyroptosis is characterized by neuronal lysis and destruction, along with the release of inflammatory factors. Autophagy is known to inhibit inflammation, and histone deacetylase-6 (HDAC6) is implicated in the regulation of both autophagy and the NLRP3 inflammasome. However, the role of these proteins in the regulation of neuronal pyroptosis in an IVH model has not been determined.</p><p><strong>Methods: </strong>In this study, an IVH mouse (6-8 weeks) model was generated via the intracerebroventricular administration of autologous blood at a volume of 40 µL/animal. After the surgical operation, we monitored the mice at various time points, assessing ventricle size via MRI. Additionally, during both the acute (3 days) and chronic (28 days) phases post-surgery, we examined neuronal cell damage and ventricular cilia, as well as neurological function, using HE staining, Nissl staining, scanning electron microscopy, and behavioral experiments such as neurological function scoring and water maze tests. Finally, we detected activation of the pyroptosis and autophagy pathway through western blotting and immunofluorescence staining.</p><p><strong>Results: </strong>Autophagy induction attenuated cerebral neuronal pyroptosis caused by acute-phase autologous blood injection. HDAC6 was implicated in regulating pyroptosis in the acute phase IVH through its influence on the transcription of nuclear factor kappa-B (NF-κB). Furthermore, HDAC6 regulates excessive autophagic activation in neurons in the chronic phase of IVH. Treatment with ricolinostat improved neurological deficits and ventricular damage during the acute phase of IVH. Moreover, it alleviated mood, memory, and learning deficits in the chronic phase of IVH while also improving PHH.</p><p><strong>Conclusions: </strong>Enhanced autophagy attenuates activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and inhibits neuronal pyroptosis in the acute phase of IVH. HDAC6 plays an important role in regulating the interaction between autophagy and pyroptosis. Ricolinostat treatment significantly attenuated the upregulation of inflammatory factors and neurological impairments induced by pyroptosis in the acute phase of IVH. In addition, ricolinostat effectively reduced excessive autophagy and apoptosis in neurons in the chronic phase and attenuated the formation of PHH.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"45"},"PeriodicalIF":5.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980967","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":"Individual-level cortical morphological network analysis in idiopathic normal pressure hydrocephalus: diagnostic and prognostic insights.","authors":"Yifeng Yang, Meijing Yan, Lianxi Sun, Xiao Liu, Xuhao Fang, Shihong Li, Guangwu Lin","doi":"10.1186/s12987-025-00653-w","DOIUrl":"https://doi.org/10.1186/s12987-025-00653-w","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic normal-pressure hydrocephalus (iNPH) is a neurodegenerative disorder characterized by treatable cognitive impairment, remains poorly understood in terms of its underlying pathological mechanisms. Cortical morphological similarity network, which quantify synchronized morphological changes across brain regions, offer novel insights into inter-individual neuroanatomical variability. This study investigates individual-level cortical morphological network patterns in iNPH, explores their diagnostic utility and prognostic value for postoperative outcomes.</p><p><strong>Methods: </strong>We enrolled 56 confirmed iNPH patients, 50 Alzheimer's disease (AD) patients, and 60 healthy controls (HC). Cortical morphological similarity networks were constructed using a morphometric inverse divergence network (MIND) framework, integrating five key cortical features: cortical thickness, mean curvature, sulcal depth, surface area, and cortical volume. Graph theory analysis was employed to quantify global and nodal network properties. Partial correlations with MMSE scores assessed network-cognition relationships. A LASSO-regularized support vector machine (SVM) classifier differentiated iNPH, AD, and HC groups using regional MIND similarity (MINDs) features. Finally, preoperative MRI-derived MINDs were integrated into a LASSO-regularized support vector regression (SVR) model to predict postoperative cognitive and gait improvements following shunt surgery.</p><p><strong>Results: </strong>Both iNPH and AD exhibited disrupted MIND network topology versus HC, including lower clustering coefficient, global efficiency, and local efficiency (all p < 0.05). Distinct spatial patterns emerged: iNPH showed localized lower values in cingulate subregions (degree centrality, node efficiency, MINDs), whereas AD demonstrated widespread alterations in fusiform, insular, and temporoparietal cortices. MMSE-associated MINDs in iNPH localized to frontostriatal circuits, contrasting with diffuse associations in AD. The multimodal classifier combining ventricular enlargement, regional brain volume, and MINDs achieved 87.00% accuracy (macro-AUC = 0.96) in three-group discrimination. Moreover, preoperative MINDs effectively predicted postoperative improvements in cognition and gait, with correlation coefficients of 0.941 and 0.889, respectively, between predicted and actual scores.</p><p><strong>Conclusions: </strong>The MIND-based morphological similarity network reveals coordinated cortical morphological alterations in iNPH and highlights its heterogeneity compared to AD. These findings offer potential biomarkers to differentiate iNPH from AD. Furthermore, the predictive efficacy of MIND-based features for postoperative outcomes underscores their utility as non-invasive preoperative tools for evaluating shunt surgery effectiveness.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"43"},"PeriodicalIF":5.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974071","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 budget for brain metabolic water production by glucose catabolism during rest, rises in activity and sleep.","authors":"Gerald A Dienel, Martin Lauritzen","doi":"10.1186/s12987-025-00647-8","DOIUrl":"https://doi.org/10.1186/s12987-025-00647-8","url":null,"abstract":"<p><p>Maintaining brain fluid homeostasis is of critical importance for creating a stable environment conducive to optimal neuronal functioning, nutrient distribution, and waste product removal. In this study, we employed previously published data on brain oxygen and glucose consumption in awake rodents or humans to quantify the metabolic water production associated with distinct pathways of glucose metabolism. It is predicted that neuronal mitochondria are the primary source of metabolic water at rest, resulting in a continuous efflux into the cytosol, interstitial fluid, and cerebrospinal fluid. Net metabolic water production is predicted to be reduced by increases in activity due to a shift in metabolism from glucose oxidation to include glycolysis in neurons and ATP hydrolysis by the major cation pumps, which involves water consumption (ATP + H₂O → ADP + Pi). In comparison, glycogenolysis, which occurs concurrently with the activation of astrocytes, potentially represents a major but previously unidentified contributor to metabolic water. Metabolic water production is dependent on the state of the brain, with a reduction of 30-40% occurring during deep sleep. Our estimates indicate that metabolic water functions as a conduit for interstitial fluid production within the brain, enabling flexible and efficient distribution of fluid that flows seamlessly from the parenchyma to the subarachnoid space and lymphatic vessels to facilitate the removal of brain waste, independent of the glymphatic system.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"22 1","pages":"44"},"PeriodicalIF":5.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005347","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}