Fluids and Barriers of the CNS最新文献

{"title":"Ablation of the choroid plexus attenuates hydrocephalus-induced parenchymal edema with moderate reduction of postnatal hippocampal neurogenesis.","authors":"Aleksandr Taranov, Florian Mayrhofer, Sage Hamm, Eric Kniffen, Joshua Peter, Felissa Wallace, Olivia Lullmann, Lucas McClain, Olga V Chechneva, Cameron Sadegh, Yu Luo","doi":"10.1186/s12987-026-00882-7","DOIUrl":"10.1186/s12987-026-00882-7","url":null,"abstract":"<p><strong>Background: </strong>Choroid plexus (ChP) produces cerebrospinal fluid (CSF) and regulates brain development and adult subventricular zone (SVZ) neurogenesis, but its role in postnatal hippocampal subgranular zone (SGZ) neurogenesis is not well understood. Infantile hydrocephalus is sometimes treated with lateral ventricle ChP cauterization, which often improves clinical symptoms without substantially reducing ventricular volumes. To understand the roles of the ChP/CSF system in normal conditions and the impact of ChP ablation or cauterization in hydrocephalus, novel tools for the manipulation of ChP-mediated CSF production are urgently needed.</p><p><strong>Methods: </strong>We first tested the ROSA26-iDTR mouse model for ChP ablation at neonatal ages, then generated a novel AAV5-CMV-DTR vector with high ChP tropism to effectively reduce ventricular volume in neonatal mice. Genetic and gene therapy approaches were compared for their extent of ChP ablation, reduction of ventricular CSF volume assessed by MRI, and impact on postnatal hippocampal neurogenesis in neonates and adults. Lastly, we tested AAV-mediated ChP ablation in a kaolin model of hydrocephalus.</p><p><strong>Results: </strong>In ROSA26-iDTR mice, ChP ablation and CSF volume reduction were robust at postnatal day (P)10-12, but ineffective at P3-5 with standard diphtheria toxin (Dtx) dosing (20 ng/g/day, 3 consecutive days). A higher dose (40 ng/g/day) at P3-5 mildly reduced CSF but caused neonatal mortality. In contrast, AAV5-CMV-DTR showed high tropism for ChP epithelium, producing a marked reduction in ventricular CSF in neonates. ChP/CSF loss in neonatal or adult mice substantially reduced neuroblasts within the SVZ, but only moderately so in the SGZ, without altering the number of proliferating or apoptotic cells. In the kaolin model, AAV-mediated ChP ablation initiated within 10 hrs after hydrocephalus induction profoundly reduced parenchymal edema and corpus callosum hyperintensity without causing ventricular collapse.</p><p><strong>Conclusions: </strong>We demonstrate a role of the ChP/CSF in maintaining the neuroblast pool in both postnatal neurogenic niches. Because ROSA26-iDTR-mediated ChP ablation is inefficient before P10, the alternative AAV5-DTR approach is relevant for both neonatal and adult ages, and is shown to be feasible for the treatment of acquired hydrocephalus. The radiographic changes in the kaolin mouse model parallels the radiographic responses reported after choroid plexus cauterization in children.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080061","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":"Establishment of an in vitro human blood-brain barrier model for antiviral screening against neurotropic viruses.","authors":"Marisol Zuniga, Alexander Herrmann, Matteo Rizzato, Michal Himl, Adriana Fontes, Hans Zischka, Romano Silvestri, Andrea Brancale, Joachim J Bugert, Ruth Brack-Werner","doi":"10.1186/s12987-026-00860-z","DOIUrl":"10.1186/s12987-026-00860-z","url":null,"abstract":"<p><strong>Background: </strong>Neurotropic viruses infect the central nervous system (CNS) resulting in severe neurological and long-term complications, including permanent cognitive impairments. However, for many of these neurotropic viruses, like tick-borne encephalitis virus (TBEV), there are no clinically approved antiviral drugs. The blood-brain barrier (BBB) is a key entry point for neurotropic viruses, as well as a barrier for drug delivery to the brain. To aid in the identification of BBB-penetrating antivirals we established a BBB-permeable antiviral screening assay (BASA).</p><p><strong>Methods: </strong>BASA combines antiviral assays with an in vitro BBB transwell model consisting of primary human brain microvascular endothelial cells (HMBEC) and pericytes (HBMVP). The combination of our in vitro BBB transwell model with astrocyte-enriched cell cultures provided a tri-culture model to investigate TBEV infection at the BBB.</p><p><strong>Results: </strong>The suitability of BASA for identifying BBB-permeable antivirals was validated by testing clinically approved anti-human immunodeficiency virus (HIV) drugs with known CNS-penetrating properties. Infection experiments reveal that TBEV crosses the intact BBB to infect astrocytic target cells. Through the application of BASA, we identify a novel BBB-permeable antiviral against TBEV (compound 3d).</p><p><strong>Conclusions: </strong>We establish a modular assay system for the early evaluation of CNS penetration potential of novel antiviral compounds. The development of tools like ours can help promote early-stage preclinical optimization of dedicated therapeutics against neurotropic viruses, while reducing the need for animal experiments.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037418","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 distortion and cerebrospinal fluid shifts in spontaneous intracranial hypotension.","authors":"Amir El Rahal, Jürgen Beck, Katharina Wolf, Florian Volz, Manou Overstijns, Niklas Lützen, Charlotte Zander, Horst Urbach, Pierre Scheffler","doi":"10.1186/s12987-026-00878-3","DOIUrl":"10.1186/s12987-026-00878-3","url":null,"abstract":"<p><strong>Background: </strong>Spinal cerebrospinal fluid (CSF) leaks in spontaneous intracranial hypotension (SIH) are assumed to cause intracranial CSF volume changes and brain sagging. The spatial pattern of CSF and brain volume changes, or shifts, remains incompletely characterized. We aimed to quantify CSF and brain shifts before and after surgical closure of spinal CSF leaks.</p><p><strong>Methods: </strong>We retrospectively analyzed 96 patients with SIH before and after surgical closure of their spinal CSF leaks. Artificial intelligence (AI)-assisted automated diffeomorphic registration and brain region segmentation of pre- and postoperative MRI imaging were used to extract a perioperative displacement map of the brain and the mean 3D displacement vector for each anatomical region. Regions were tested for significant changes using Hotelling's T² and compared against a healthy control cohort (n = 61) processed identically.</p><p><strong>Results: </strong>When comparing pre- and postoperative scans, brain structures demonstrated a consistent, predominantly upward-outward shift. Most major brain regions exhibited small, but statistically significant movement, with the highest magnitude seen in the parietal lobes and the left lateral ventricle (> 0.7 mm, p < 0.0001). Functionally connected regions, such as those within the fronto-limbic and visual networks, exhibited shifts in various directions, resulting in regional deformation. Displacement exceeded that of healthy controls roughly threefold (0.51 versus 0.16 mm across regions).</p><p><strong>Conclusion: </strong>Surgical CSF-leak closure in SIH leads to postoperative brain shift and tectonic-like deformation quantifiable on MRI. AI-assisted measurements reveal subtle brain movements and distortions, which could contribute to understanding of spinal leak pathophysiology and complement clinical assessment during follow-up.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059613","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":"No evidence of major integrative brain clearance impairment in an Alzheimer´s disease model of transgenic APPswe/PS1dE9 mice.","authors":"Luisa Müller, Charlotte Köhler, Tobias Lindner, Stefan Polei, Brigitte Vollmar, Marc-André Weber, Bernd J Krause, Timo Kirschstein, Katrin Porath, Nadja Engel, Stefan Teipel, Alexander Radbruch, Katerina Deike, Angela Kuhla","doi":"10.1186/s12987-026-00872-9","DOIUrl":"10.1186/s12987-026-00872-9","url":null,"abstract":"<p><strong>Background: </strong>Brain clearance pathways via the interstitial fluid and cerebrospinal fluid are essential for maintaining homeostasis and removing metabolic waste. Disruptions in these processes are linked to neurodegenerative diseases, particularly Alzheimer's Disease (AD), where an imbalance between amyloid β (Aβ) production and clearance leads to cerebral amyloidosis. Although AD research continues to rely heavily on murine models, including APPswe/PS1dE9 mice, it remains unclear to what extent these models replicate the deficits in brain clearance observed in human AD.</p><p><strong>Methods: </strong>We examined AD pathology in transgenic APPswe/PS1dE9 (tg) mice and wildtype (wt) littermates at six, nine and twelve months using immunohistochemistry for Aβ plaques (6E10⁺) and activated microglia (Iba1⁺). To assess integrative parameters contributing to brain clearance, we applied two complementary approaches. First, we performed daytime-dependent intrahippocampal injections of a fluorescent tracer in six-month-old tg and wt mice, followed by histological analysis of tracer dispersion 1 h and 3 h after injection. Second, we present a novel, longitudinal and non-invasive approach utilizing washout kinetics of intravenously administered gadolinium-based contrast agents (GBCA) as an integrative proxy to assess brain clearance dynamics. In this novel approach DOTAREM^® was administered intravenously and imaging was done with anesthetized tg and wt mice at nine and twelve months of age. Integrity of the blood-brain-barrier was further evaluated via western blot analysis of occludin protein expression.</p><p><strong>Results: </strong>Despite tg mice displayed characteristic AD-like phenotype, with significant, age-dependent Aβ plaque deposition and neuroinflammation no significant differences in the integrative GBCA washout kinetics were detected between wt and tg mice, suggesting that no major deficits in the combined clearance pathways are present. However, contrast-agent uptake showed a general age-dependent increase consistent with aging-related changes known from human studies.</p><p><strong>Conclusion: </strong>Our findings indicate that the APPswe/PS1dE9 mouse model does not exhibit evidence of major integrative brain clearance impairment, despite this being a hallmark of sporadic AD in humans. These results suggest limitations of this model for studying clearance-related mechanisms of late-onset AD, which should be acknowledged when planning future studies using this murine model.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905491","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 parenchyma deformation and strain in patients with spontaneous intracranial hypotension.","authors":"Amir El Rahal, Jürgen Beck, Katharina Wolf, Florian Volz, Manou Overstijns, Niklas Lützen, Charlotte Zander, Horst Urbach, Pierre Scheffler","doi":"10.1186/s12987-026-00865-8","DOIUrl":"10.1186/s12987-026-00865-8","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous intracranial hypotension (SIH) is mainly associated with orthostatic headache but can also cause cognitive impairment, with symptoms mimicking behavioral-type frontotemporal dementia in severe cases. SIH is caused by a spinal cerebrospinal fluid (CSF) leak and can lead to brain sagging. The specific brain regions affected by this motion, their deformation, and the magnitude of the associated mechanical strain have not been quantitatively characterized. We investigated whether brain MRI in patients with SIH shows quantifiable strain, expansion, and compression of brain structures by comparing images before and after surgical occlusion of a spinal leak.</p><p><strong>Methods: </strong>We performed a retrospective analysis of 96 patients with SIH who underwent surgical closure of a spinal CSF leak. We performed AI-assisted diffeomorphic registration of pre- and postoperative MRI. From the resulting displacement maps, we calculated the Jacobian determinant as an indicator of expansion and contraction, and the von Mises equivalent deviatoric strain as an indicator of distortion and shearing in brain regions. Results were compared with 61 healthy adults scanned twice over a comparable interval, and correlated with perioperative headache, quality-of-life and cognitive scores.</p><p><strong>Results: </strong>Ventricles and transverse sinuses showed relevant perioperative expansion and contraction, respectively. Beyond these expected volumetric changes, significant deviatoric strain was observed in temporomesial and frontal structures, including the temporal poles (right/ left: 8.6/ 8.7%), hippocampus (9.0/ 9.8%), and basal forebrain (9.9/ 9.8%) (p < 0.001 for all), despite only moderate volumetric change in these regions. Deformation substantially exceeded that of healthy controls. Whole-brain strain showed a modest positive association with perioperative improvement in headache burden, whereas analyses of cognitive outcome were underpowered.</p><p><strong>Conclusion: </strong>SIH is associated with quantifiable regional brain deformation resulting in region-specific mechanical strain. Elevated strain in fronto-limbic and temporomesial regions, implicated in behavioral and cognitive regulation, suggests a network-level mechanical effect that may contribute to the clinical presentation observed in severe SIH.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850102","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":"Integrative multi-omics profiling reveals an association between lipid metabolism dysregulation and bortezomib-induced cerebral hemorrhage in zebrafish.","authors":"Yulian Li, Si Dong, Hao Cheng, Yunyun Du, Shanshan Zhu, Fasheng Liu, Yongliang Zheng, Ting Ding, Wenfeng He, Xiaoping Wang, Zigang Cao, Junquan Zeng","doi":"10.1186/s12987-026-00867-6","DOIUrl":"10.1186/s12987-026-00867-6","url":null,"abstract":"<p><p>Bortezomib (BTZ), a first-generation proteasome inhibitor, serves as a cornerstone chemotherapeutic agent for Multiple Myeloma (MM), with its clinical application in oncology expanding rapidly in recent years. Using vascular-specific transgenic zebrafish models, we systematically evaluated BTZ-induced toxicity at 4-5 mg/L gradient concentrations and its underlying molecular mechanisms. We found 72-hour BTZ exposure triggered significant intracerebral hemorrhage in zebrafish larvae with concentration-dependent severity, accompanied by cerebrovascular disruption, tight junction gene downregulation, lipid metabolism disorder, ROS accumulation and antioxidant enzyme response, and abnormal nitric oxide activation. This study first reveals that BTZ-induced intracerebral hemorrhage is closely associated with lipid metabolism dysregulation, highlighting lipid disturbance as a potential contributor to cerebrovascular injury.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080038","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 effect of magnetic interference by magnetic resonance imaging on programmable shunt valves in patients with normal pressure hydrocephalus: a systematic review and pooled analysis.","authors":"Virensinh Rathod, Darius Kalasauskas, Florian Ringel, Harroop Bola, Daniele S C Ramsay, Karanjot Chhatwal, Srikar R Namireddy, Sree Kanakala, Iihan Ali, Dillon Nanoo, Eeshan Gangwani, Terrenjit Gill, Ayush Jha, Ahmed Salih, Madhur Varadpande, Abith G Kamath, Ahkash Thavarajasingam, Dragan Jankovic, Andreas Kramer, Santhosh G Thavarajasingam","doi":"10.1186/s12987-026-00837-y","DOIUrl":"https://doi.org/10.1186/s12987-026-00837-y","url":null,"abstract":"<p><strong>Introduction: </strong>Normal pressure hydrocephalus (NPH) is a cause of neurological impairment, with programmable shunt valves serving as the standard treatment. However, magnetic interference can result in altered pressure settings, affecting valve functionality.</p><p><strong>Research question: </strong>This systematic review investigates the effects of magnetic resonance imaging (MRI) on programmable shunt valves in NPH patients.</p><p><strong>Material and methods: </strong>Conducted in adherence to PRISMA guidelines, an extensive literature search across PubMed and Embase databases from January 2000 to January 2025, was performed. Studies evaluating the impact of MRI at 1.5T and 3T field strengths on valve settings were included. Valve reprogrammability and outcomes were analysed, with statistical comparisons across MRI strengths and valve types using Mann-Whitney U and ANOVA tests.</p><p><strong>Results: </strong>The pooled analysis included 475 NPH patients across 11 studies. Valve setting alteration was required in 44.2% of cases following 1.5T exposure and 55.2% after 3T exposure, with no statistically significant difference between field strengths (p > 0.05). Valve type analysis revealed that the Codman Hakim valve exhibited the highest incidence of setting changes (37.05% at 3T). However, differences in valve setting changes between manufacturers were not statistically significant (p > 0.05).</p><p><strong>Discussion and conclusion: </strong>Magnetic interference from MRI can disrupt programmable shunt valves in NPH patients. While 3T MRI shows a slightly higher incidence of valve setting changes than 1.5T, the difference is not significant. Further research is required to assess long- term clinical implications and standardize MRI protocols to mitigate variability in outcomes.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762635","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":"Piezo1-Src signaling rapidly disrupts brain endothelial barrier integrity.","authors":"Yu Iida, Taisuke Akimoto, Kagemichi Nagao, Akane Nagasako, Michiko Endo, Yayoi Kimura, Makoto Ohtake, Tetsuya Yamamoto, Yoshihiro Ishikawa, Masanari Umemura","doi":"10.1186/s12987-026-00859-6","DOIUrl":"10.1186/s12987-026-00859-6","url":null,"abstract":"<p><strong>Background: </strong>Blood-brain barrier integrity is essential for central nervous system homeostasis, yet the mechanisms underlying ultra-acute barrier dysfunction after abrupt hemodynamic changes remain incompletely understood. Piezo1 is a mechanosensitive Ca²⁺ channel expressed in endothelial cells and activated by mechanical stimuli such as shear stress, but its contribution to rapid brain endothelial barrier disruption remains unclear. We investigated whether Piezo1 activation induces an ultra-acute disruption of the endothelial barrier and explored the underlying signaling mechanisms.</p><p><strong>Methods: </strong>Human brain microvascular endothelial cells (HBEC-5i) were stimulated with the Piezo1 agonist Yoda1 in the presence or absence of the Src inhibitor saracatinib, followed by barrier-function assessment and phosphoproteomic profiling. To assess in vivo relevance, vascular permeability was evaluated within minutes after reperfusion in a mouse cerebral ischemia-reperfusion model treated with the mechanosensitive channel inhibitor GsMTx4.</p><p><strong>Results: </strong>Comprehensive phosphoproteomic profiling after Piezo1 activation revealed enrichment of phosphorylation events associated with cell junctions, adhesion, and cytoskeletal organization. Yoda1 induced rapid phosphorylation of junction-associated proteins, including occludin at Tyr287, and caused acute barrier disruption in HBEC-5i cells. Saracatinib attenuated occludin Tyr287 phosphorylation and preserved barrier integrity, supporting the involvement of Src-family kinase-sensitive signaling in this response. In mice, GsMTx4 significantly attenuated vascular permeability within minutes after reperfusion, consistent with the in vitro observations and supporting a role for mechanosensitive channel-associated signaling in ultra-acute blood-brain barrier leakage immediately after flow restoration.</p><p><strong>Conclusions: </strong>This study provides the first phosphoproteomic characterization of rapid phosphorylation changes associated with Piezo1 activation in human brain endothelial cells. Guided by these phosphoproteomic signatures, our data support the involvement of saracatinib-sensitive signaling, accompanied by occludin Tyr287 phosphorylation, in rapid endothelial barrier disruption. These findings suggest that Piezo1-associated signaling may contribute to ultra-acute BBB dysfunction and provide a rational for further investigation in the context of abrupt hemodynamic stress and cerebral revascularization.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037374","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":"Pulsatile intraspinal pressure drives post-traumatic syringomyelia: evidence supporting the CSF pulsatile pressure dynamic equilibrium hypothesis.","authors":"Chenghua Yuan, Fan Yuan, Chao Chang, Jiachen Wang, Zuowei Wang, Xingwen Wang, Hao Wu, Zan Chen, Fengzeng Jian, Jian Guan","doi":"10.1186/s12987-026-00846-x","DOIUrl":"10.1186/s12987-026-00846-x","url":null,"abstract":"<p><strong>Objective: </strong>Recent discoveries focused on the role of intraspinal pressure (ISP) in metabolite clearance after spinal cord injury (SCI) have initiated intense research on CSF inflow and outflow pathways. This study aimed to investigate whether the pulsatile ISP wave serves as the primary driver of posttraumatic syringomyelia (PTS) formation and progression, and to determine if a novel subarachnoid‑subarachnoid (S‑S) bypass procedure can effectively attenuate this abnormal pulsatile ISP wave in affected PTS patients.</p><p><strong>Methods: </strong>In this prospective cohort study of patients with PTS, ISP across the injury site was monitored intraoperatively both before and after placement of the S-S bypass tube. Neurological impairment was assessed using standardized scales at baseline, one year postoperatively, and at the final follow-up. A logistic regression model was used to analyze prognostic factors associated with surgical outcomes.</p><p><strong>Result: </strong>All 64 enrolled patients underwent S-S bypass surgery; 54 (84.4%) had a history of incomplete SCI. After a mean follow-up of 23.6 months (range: 12-36 months), 46 patients (71.9%) showed neurological improvement. Multivariate logistic regression identified three independent predictors of positive recovery: the pre-bypass ISP gradient across the injury site (OR = 2.228, P = 0.036), the pre-bypass ISP amplitude measured cranial to the injury site (OR = 4.269, P = 0.031) and a bypass tube spanning vertebral levels (OR = 0.331, P = 0.020). Receiver operating characteristic (ROC) curve analysis determined the optimal predictive cut-offs for these parameters. A pre-bypass ISP gradient > 1.5 mmHg showed a sensitivity of 93.48% and a specificity of 66.67%, a pre-bypass ISP amplitude measured cranial to the injury site >3.5 mmHg yielded a sensitivity of 82.61% and a specificity of 94.44%, while a bypass spanning < 5.5 vertebral levels showed a sensitivity of 100% and a specificity of 44.44%.</p><p><strong>Conclusions: </strong>S-S bypass procedure can effectively reduce abnormal Pulsatile Pressure Wave in patients with PTS. This study demonstrates that a pre-bypass ISP gradient > 1.5 mmHg across the injury site, a pre-bypass ISP amplitude >3.5 mmHg measured cranial to the injury site and a bypass conduit spanning < 5.5 vertebral levels are strong, independent predictors of neurological recovery after S-S bypass surgery for posttraumatic syringomyelia.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850094","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":"Transient weakening of the blood-brain barrier in neonatal mice.","authors":"Amira Sayed Hanafy, Dirk Dietrich","doi":"10.1186/s12987-026-00858-7","DOIUrl":"10.1186/s12987-026-00858-7","url":null,"abstract":"<p><strong>Background: </strong>Tight junctions (TJs) are a major structural component of the blood-brain barrier (BBB), contributing to brain homeostasis by restricting paracellular diffusion. Although BBB maturation begins during embryogenesis, the timing and dynamics of functional barrier maturation perinatally remain unclear. This question is particularly relevant for the striatum, a metabolically demanding brain region that undergoes rapid postnatal maturation and is vulnerable to neonatal injury.</p><p><strong>Methods: </strong>We investigated developmental dynamics of BBB tracer permeability in mouse striatum using in situ microperfusion of capillaries (ISMICAP) combined with two-photon microscopy. Small-molecule tracers were applied from late embryonic (E18) to adolescent (P25) stages. Bovine serum albumin (BSA) was applied as a macromolecular tracer at P2 and P25.</p><p><strong>Results: </strong>Small-molecule tracers, namely 7-hydroxycoumarin-3-carboxylic acid (7HCC), sulforhodamine 101 (SR101), and biocytin-tetramethylrhodamine, revealed a pronounced but transient increase in extravascular fluorescence during the neonatal phase (P0-P2), followed by progressive restriction by P12 and P25. During the neonatal permeability window, 7HCC labeled perivascular cells located ~ 2.8 μm from the endothelium and distinct from NT500/525-labeled pericytes, whereas SR101 accumulated within endothelial cytoplasm, indicating tracer-specific vascular and perivascular accumulation patterns. The membrane probe FM1-43 showed a similar temporal pattern, with enhanced diffusion to abluminal membranes and labeling of pericyte-like mural cells. In contrast, BSA showed low extravascular fluorescence at P2 comparable to P25, indicating that increased neonatal small-molecule permeability did not extend to BSA-sized macromolecules. At P25, small-molecule tracer permeability was higher in the striatum than in the cortex, whereas FM1-43 showed the opposite regional pattern.</p><p><strong>Conclusions: </strong>BBB maturation in the striatum is not a linear tightening process but includes a transient neonatal phase of increased TJ-associated permeability to small-molecule tracers, while remaining restrictive to BSA-sized macromolecules. Although tracer-specific vascular and perivascular accumulation patterns were observed, the overall temporal profile supports a discrete perinatal window of decreased barrier restriction. This dynamic permeability window may reflect physiological remodeling of barrier function during the perinatal transition. Defining this window mechanistically may improve understanding of neonatal brain vulnerability and may inform strategies for temporally targeted CNS drug delivery.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721119","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}