Fluids and Barriers of the CNS最新文献

{"title":"Oxidative stress alters mitochondrial homeostasis in isolated brain capillaries.","authors":"Gopal V Velmurugan, Hemendra J Vekaria, Anika M S Hartz, Björn Bauer, W Brad Hubbard","doi":"10.1186/s12987-024-00579-9","DOIUrl":"https://doi.org/10.1186/s12987-024-00579-9","url":null,"abstract":"<p><strong>Background: </strong>Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.</p><p><strong>Methods: </strong>To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which we used isolated brain capillaries from transgenic mice that express dendra2 green specifically in mitochondria (mtD2g). Isolated brain capillaries were incubated with 2,2'-azobis-2-methyl-propanimidamide dihydrochloride (AAPH) or hydrogen peroxide (H₂O₂) to induce oxidative stress through lipid peroxidation. Following the oxidative insult, mitochondrial bioenergetics were measured using the Seahorse XFe96 flux analyzer, and mitochondrial dynamics were measured using confocal microscopy with Imaris software.</p><p><strong>Results: </strong>We optimized brain capillary isolation with intact endothelial cell tight-junction and pericyte integrity. Further, we demonstrate consistency of the capillary isolation process and cellular enrichment of the isolated capillaries. Mitochondrial bioenergetics and morphology assessments were optimized in isolated brain capillaries. Finally, we found that oxidative stress significantly decreased mitochondrial respiration and altered mitochondrial morphology in brain capillaries, including mitochondrial volume and count.</p><p><strong>Conclusions: </strong>Following ex vivo isolation of brain capillaries, we confirmed the stability of mitochondrial parameters, demonstrating the feasibility of this newly developed platform. We also demonstrated that oxidative stress has profound effects on mitochondrial homeostasis in isolated brain capillaries. This novel method can be used to evaluate pharmacological interventions to target oxidative stress or mitochondrial dysfunction in cerebral small vessel disease and neurovascular pathophysiology as major players in neurodegenerative disease.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"81"},"PeriodicalIF":5.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461613","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":"Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries.","authors":"Lars Willas Dreyer, Anders Eklund, Marie E Rognes, Jan Malm, Sara Qvarlander, Karen-Helene Støverud, Kent-Andre Mardal, Vegard Vinje","doi":"10.1186/s12987-024-00582-0","DOIUrl":"https://doi.org/10.1186/s12987-024-00582-0","url":null,"abstract":"<p><strong>Background: </strong>Infusion testing is an established method for assessing CSF resistance in patients with idiopathic normal pressure hydrocephalus (iNPH). To what extent the increased resistance is related to the glymphatic system is an open question. Here we introduce a computational model that includes the glymphatic system and enables us to determine the importance of (1) brain geometry, (2) intracranial pressure, and (3) physiological parameters on the outcome of and response to an infusion test.</p><p><strong>Methods: </strong>We implemented a seven-compartment multiple network porous medium model with subject specific geometries from MR images using the finite element library FEniCS. The model consists of the arterial, capillary and venous blood vessels, their corresponding perivascular spaces, and the extracellular space (ECS). Both subject specific brain geometries and subject specific infusion tests were used in the modeling of both healthy adults and iNPH patients. Furthermore, we performed a systematic study of the effect of variations in model parameters.</p><p><strong>Results: </strong>Both the iNPH group and the control group reached a similar steady state solution when subject specific geometries under identical boundary conditions was used in simulation. The difference in terms of average fluid pressure and velocity between the iNPH and control groups, was found to be less than 6% during all stages of infusion in all compartments. With subject specific boundary conditions, the largest computed difference was a 75% greater fluid speed in the arterial perivascular space (PVS) in the iNPH group compared to the control group. Changes to material parameters changed fluid speeds by several orders of magnitude in some scenarios. A considerable amount of the CSF pass through the glymphatic pathway in our models during infusion, i.e., 28% and 38% in the healthy and iNPH patients, respectively.</p><p><strong>Conclusions: </strong>Using computational models, we have found the relative importance of subject specific geometries to be less important than individual differences in resistance as measured with infusion tests and model parameters such as permeability, in determining the computed pressure and flow during infusion. Model parameters are uncertain, but certain variations have large impact on the simulation results. The computations resulted in a considerable amount of the infused volume passing through the brain either through the perivascular spaces or the extracellular space.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"82"},"PeriodicalIF":5.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461612","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":"Ex vivo nanoscale abluminal mapping of putative cargo receptors at the blood-brain barrier of expanded brain capillaries.","authors":"Mikkel Roland Holst, Mette Richner, Pernille Olsgaard Arenshøj, Parvez Alam, Kathrine Hyldig, Morten Schallburg Nielsen","doi":"10.1186/s12987-024-00585-x","DOIUrl":"https://doi.org/10.1186/s12987-024-00585-x","url":null,"abstract":"<p><p>Receptor mediated transport of therapeutic antibodies through the blood-brain barrier (BBB) give promise for drug delivery to alleviate brain diseases. We developed a low-cost method to obtain nanoscale localization data of putative cargo receptors. We combine existing ex vivo isolation methods with expansion microscopy (ExM) to analyze receptor localizations in brain microcapillaries. Using this approach, we show how to analyze receptor localizations in endothelial cells of brain microcapillaries in relation to the abluminal marker collagen IV. By choosing the thinnest capillaries, microcapillaries for analysis, we ensure the validity of collagen IV as an abluminal marker. With this tool, we confirm transferrin receptors as well as sortilin to be both luminally and abluminally localized. Furthermore, we identify basigin to be an abluminal receptor. Our methodology can be adapted to analyze different types of isolated brain capillaries and we anticipate that this approach will be very useful for the research community to gain new insight into cargo receptor trafficking in the slim brain endothelial cells to elucidate novel paths for future drug design.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"80"},"PeriodicalIF":5.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461611","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":"iPSC-derived blood-brain barrier modeling reveals APOE isoform-dependent interactions with amyloid beta.","authors":"Yunfeng Ding, Sean P Palecek, Eric V Shusta","doi":"10.1186/s12987-024-00580-2","DOIUrl":"10.1186/s12987-024-00580-2","url":null,"abstract":"<p><strong>Background: </strong>Three common isoforms of the apolipoprotein E (APOE) gene - APOE2, APOE3, and APOE4 - hold varying significance in Alzheimer's Disease (AD) risk. The APOE4 allele is the strongest known genetic risk factor for late-onset Alzheimer's Disease (AD), and its expression has been shown to correlate with increased central nervous system (CNS) amyloid deposition and accelerated neurodegeneration. Conversely, APOE2 is associated with reduced AD risk and lower CNS amyloid burden. Recent clinical data have suggested that increased blood-brain barrier (BBB) leakage is commonly observed among AD patients and APOE4 carriers. However, it remains unclear how different APOE isoforms may impact AD-related pathologies at the BBB.</p><p><strong>Methods: </strong>To explore potential impacts of APOE genotypes on BBB properties and BBB interactions with amyloid beta, we differentiated isogenic human induced pluripotent stem cell (iPSC) lines with different APOE genotypes into both brain microvascular endothelial cell-like cells (BMEC-like cells) and brain pericyte-like cells. We then compared the effect of different APOE isoforms on BBB-related and AD-related phenotypes. Statistical significance was determined via ANOVA with Tukey's post hoc testing as appropriate.</p><p><strong>Results: </strong>Isogenic BMEC-like cells with different APOE genotypes had similar trans-endothelial electrical resistance, tight junction integrity and efflux transporter gene expression. However, recombinant APOE4 protein significantly impeded the \"brain-to-blood\" amyloid beta 1-40 (Aβ40) transport capabilities of BMEC-like cells, suggesting a role in diminished amyloid clearance. Conversely, APOE2 increased amyloid beta 1-42 (Aβ42) transport in the model. Furthermore, we demonstrated that APOE-mediated amyloid transport by BMEC-like cells is dependent on LRP1 and p-glycoprotein pathways, mirroring in vivo findings. Pericyte-like cells exhibited similar APOE secretion levels across genotypes, yet APOE4 pericyte-like cells showed heightened extracellular amyloid deposition, while APOE2 pericyte-like cells displayed the least amyloid deposition, an observation in line with vascular pathologies in AD patients.</p><p><strong>Conclusions: </strong>While APOE genotype did not directly impact general BMEC or pericyte properties, APOE4 exacerbated amyloid clearance and deposition at the model BBB. Conversely, APOE2 demonstrated a potentially protective role by increasing amyloid transport and decreasing deposition. Our findings highlight that iPSC-derived BBB models can potentially capture amyloid pathologies at the BBB, motivating further development of such in vitro models in AD modeling and drug development.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"79"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406211","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":"Aging alters the expression of trophic factors and tight junction proteins in the mouse choroid plexus.","authors":"Jayanarayanan Sadanandan, Monica Sathyanesan, Samuel S Newton","doi":"10.1186/s12987-024-00574-0","DOIUrl":"10.1186/s12987-024-00574-0","url":null,"abstract":"<p><strong>Background: </strong>The choroid plexus (CP) is an understudied tissue in the central nervous system and is primarily implicated in cerebrospinal fluid (CSF) production. CP also produces numerous neurotrophic factors (NTF) which circulate to different brain regions. Regulation of NTFs in the CP during natural aging is largely unknown. Here, we investigated the age and gender-specific transcription of NTFs along with the changes in the tight junctional proteins (TJPs) and the water channel protein Aquaporin (AQP1).</p><p><strong>Methods: </strong>Male and female mice were used for our study. Age-related transcriptional changes were analyzed using quantitative PCR at three different time points: mature adult, middle-aged, and aged. Transcriptional changes during aging were further confirmed with digital droplet PCR. Additionally, we used immunohistochemical analysis (IHC) for the evaluation of in vivo protein expression. We further investigated the cellular phenotype of these NTFS, TJP, and water channel proteins in the mouse CP by co-labeling them with the classical vascular marker, Isolectin B4, and epithelial cell marker, Plectin.</p><p><strong>Results: </strong>Aging significantly altered NTF gene expression in the CP. Brain-derived neurotrophic factor (BDNF), Midkine (MDK), VGF, Insulin-like growth factor (IGF1), IGF2, Klotho (KL), Erythropoietin (EPO), and its receptor (EPOR) were reduced in the aged CP of males and females. Vascular endothelial growth factor (VEGF) transcription was gender-specific; in males, gene expression was unchanged in the aged CP, while females showed an age-dependent reduction. Age-dependent changes in VEGF localization were evident, from vasculature to epithelial cells. IGF2 and klotho localized in the basolateral membrane of the CP and showed an age-dependent reduction in epithelial cells. Water channel protein AQP1 localized in the tip of epithelial cells and showed an age-related reduction in mRNA and protein levels. TJP's JAM, CLAUDIN1, CLAUDIN2 and CLAUDIN5 were reduced in aged mice.</p><p><strong>Conclusions: </strong>Our study highlights transcriptional level changes in the CP during aging. The age-related transcriptional changes exhibit similarities as well as gene-specific differences in the CP of males and females. Altered transcription of the water channel protein AQP1 and TJPs could be involved in reduced CSF production during aging. Importantly, reduction in the neurotrophic factors and longevity factor Klotho can play a role in regulating brain aging.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"77"},"PeriodicalIF":5.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344463","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":"Human iPSC-derived pericyte-like cells carrying APP Swedish mutation overproduce beta-amyloid and induce cerebral amyloid angiopathy-like changes.","authors":"Ying-Chieh Wu, Šárka Lehtonen, Kalevi Trontti, Riitta Kauppinen, Pinja Kettunen, Ville Leinonen, Markku Laakso, Johanna Kuusisto, Mikko Hiltunen, Iiris Hovatta, Kristine Freude, Hiramani Dhungana, Jari Koistinaho, Taisia Rolova","doi":"10.1186/s12987-024-00576-y","DOIUrl":"10.1186/s12987-024-00576-y","url":null,"abstract":"<p><strong>Background: </strong>Patients with Alzheimer's disease (AD) frequently present with cerebral amyloid angiopathy (CAA), characterized by the accumulation of beta-amyloid (Aβ) within the cerebral blood vessels, leading to cerebrovascular dysfunction. Pericytes, which wrap around vascular capillaries, are crucial for regulating cerebral blood flow, angiogenesis, and vessel stability. Despite the known impact of vascular dysfunction on the progression of neurodegenerative diseases, the specific role of pericytes in AD pathology remains to be elucidated.</p><p><strong>Methods: </strong>To explore this, we generated pericyte-like cells from human induced pluripotent stem cells (iPSCs) harboring the Swedish mutation in the amyloid precursor protein (APPswe) along with cells from healthy controls. We initially verified the expression of classic pericyte markers in these cells. Subsequent functional assessments, including permeability, tube formation, and contraction assays, were conducted to evaluate the functionality of both the APPswe and control cells. Additionally, bulk RNA sequencing was utilized to compare the transcriptional profiles between the two groups.</p><p><strong>Results: </strong>Our study reveals that iPSC-derived pericyte-like cells (iPLCs) can produce Aβ peptides. Notably, cells with the APPswe mutation secreted Aβ1-42 at levels ten-fold higher than those of control cells. The APPswe iPLCs also demonstrated a reduced ability to support angiogenesis and maintain barrier integrity, exhibited a prolonged contractile response, and produced elevated levels of pro-inflammatory cytokines following inflammatory stimulation. These functional changes in APPswe iPLCs correspond with transcriptional upregulation in genes related to actin cytoskeleton and extracellular matrix organization.</p><p><strong>Conclusions: </strong>Our findings indicate that the APPswe mutation in iPLCs mimics several aspects of CAA pathology in vitro, suggesting that our iPSC-based vascular cell model could serve as an effective platform for drug discovery aimed to ameliorate vascular dysfunction in AD.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"78"},"PeriodicalIF":5.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344464","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":"NX210c drug candidate peptide strengthens mouse and human blood-brain barriers.","authors":"Chris Greene, Nicolas Rebergue, Gwen Fewell, Damir Janigro, Yann Godfrin, Matthew Campbell, Sighild Lemarchant","doi":"10.1186/s12987-024-00577-x","DOIUrl":"https://doi.org/10.1186/s12987-024-00577-x","url":null,"abstract":"<p><strong>Background: </strong>Alterations of blood-brain barrier (BBB) and blood-spinal cord barrier have been documented in various animal models of neurodegenerative diseases and in patients. Correlations of these alterations with functional deficits suggest that repairing barriers integrity may represent a disease-modifying approach to prevent neuroinflammation and neurodegeneration induced by the extravasation of blood components into the parenchyma. Here, we screened the effect of a subcommissural organ-spondin-derived peptide (NX210c), known to promote functional recovery in several models of neurological disorders, on BBB integrity in vitro and in vivo.</p><p><strong>Methods: </strong>In vitro, bEnd.3 endothelial cell (EC) monolayers and two different primary human BBB models containing EC, astrocytes and pericytes, in static and microfluidic conditions, were treated with NX210c (1-100 µM), or its vehicle, for 4 h and up to 5 days. Tight junction (TJ) protein levels, permeability to dextrans and transendothelial electrical resistance (TEER) were evaluated. In vivo, young and old mice (3- and 21-month-old, respectively) were treated daily intraperitoneally with NX210c at 10 mg/kg or its vehicle for 5 days and their brains collected at day 6 to measure TJ protein levels by immunohistochemistry.</p><p><strong>Results: </strong>NX210c induced an increase in claudin-5 protein expression after 24-h and 72-h treatments in mouse EC. Occludin level was also increased after a 24-h treatment. Accordingly, NX210c decreased by half the permeability of EC to a 40-kDa FITC-dextran and increased TEER. In the human static BBB model, NX210c increased by ∼ 25% the TEER from 3 to 5 days. NX210c also increased TEER in the human 3D dynamic BBB model after 4 h, which was associated with a reduced permeability to a 4-kDa FITC-dextran. In line with in vitro results, after only 5 days of daily treatments in mice, NX210c restored aging-induced reduction of claudin-5 and occludin levels in the hippocampus, and also in the cortex for occludin.</p><p><strong>Conclusions: </strong>In summary, we have gathered preclinical data showing the capacity of NX210c to strengthen BBB integrity. Through this property, NX210c holds great promises of being a disease-modifying treatment for several neurological disorders with high unmet medical needs.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"21 1","pages":"76"},"PeriodicalIF":5.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344465","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":"Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier","authors":"Laura Fritzen, Katharina Wienken, Lelia Wagner, Magdalena Kurtyka, Katharina Vogel, Jakob Körbelin, Sascha Weggen, Gert Fricker, Claus U. Pietrzik","doi":"10.1186/s12987-024-00573-1","DOIUrl":"https://doi.org/10.1186/s12987-024-00573-1","url":null,"abstract":"The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands’ route across endothelial cells in vitro. The use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1). We showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß42 peptide levels after mLRP1_DIV* mediated transport across a co-cultured endothelial monolayer. Together, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it’s release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"44 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on “Transient intracranial pressure elevations (B waves) associated with sleep apnea”: the neglected role of cyclic alternating pattern","authors":"Carlotta Mutti, Clara Rapina, Francesco Rausa, Giulia Balella, Dario Bottignole, Marcello Giuseppe Maggio, Liborio Parrino","doi":"10.1186/s12987-024-00569-x","DOIUrl":"https://doi.org/10.1186/s12987-024-00569-x","url":null,"abstract":"&lt;p&gt;Riedel et al. recently published an interesting paper on the association between intracranial pressure (ICP) elevation, measured through the Lundberg B waves, and sleep apnea in a group of patients with idiopathic intracranial hypertension (IIH) and hydrocephalus [1].&lt;/p&gt;&lt;p&gt;ICP B waves are defined as short, repetitive elevation of intracranial pressure of up to 50 mmHg with a frequency of 0.5-2 waves/min, which are typically observed in patients with IIH, but can also be measured in subjects with normal intracranial pressure [2].&lt;/p&gt;&lt;p&gt;Obstructive sleep apnea (OSA) is a multi-systemic syndrome characterized by phasic interruptions of airflow during sleep, leading to severe sleep fragmentation and cardiovascular consequences, presenting a typical 20-40 s periodicity (Panel A, Fig. 1).&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 1&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12987-024-00569-x/MediaObjects/12987_2024_569_Fig1_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"383\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12987-024-00569-x/MediaObjects/12987_2024_569_Fig1_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;&lt;b&gt;A&lt;/b&gt; Vertical integration between CAP fluctuations during NREM sleep, respiratory events, oxygen desaturation and pulse rate dynamic in a patient affected by OSA. &lt;b&gt;B&lt;/b&gt; figure published in Riedel et al., 2023 showing the vertical integration between ICP oscillations, obstructive apnea events and sleep fragmentation. &lt;b&gt;C&lt;/b&gt; example of physiological CAP fluctuations during NREM sleep in a healthy subject. &lt;b&gt;D&lt;/b&gt; example of stable NREM with no CAP intrusion&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;p&gt;According to Riedel et al. [1], there is an interesting association between ICP B waves and sleep apnea. The overlap of B waves with repetitive respiratory events induces a further increase in the ICP elevation (See Panel B in Fig. 1). The synusoidal pattern becomes particularly relevant during obstructive respiratory events (compared to central-type events), whereas the introduction of CPAP leads to overall reduction of phasic ICP elevations.&lt;/p&gt;&lt;p&gt;Riedel et al. [1] show the temporal coupling between ICP fluctuations, nasal airflow flattening, thorax and abdomen activity changes, SatO2% oscillations and sleep stage dynamics.&lt;/p&gt;&lt;p&gt;In Panel B (Fig. 1) severe sleep fragmentation characterized by numerous brief awakening lasting &lt; 2 min is recognizable in a patient with idiopathic normal pressure hydrocephalus and OSA during stage N2 of NREM sleep.&lt;/p&gt;&lt;p&gt;It is known that OSA is closely associated cyclic alternating pattern (CAP) oscillations, including not only fast but also slow-wave arous","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"7 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood–brain barrier breakdown in dementia with Lewy bodies","authors":"Jinghuan Gan, Ziming Xu, Zhichao Chen, Shuai Liu, Hao Lu, Yajie Wang, Hao Wu, Zhihong Shi, Huijun Chen, Yong Ji","doi":"10.1186/s12987-024-00575-z","DOIUrl":"https://doi.org/10.1186/s12987-024-00575-z","url":null,"abstract":"Blood–brain barrier (BBB) dysfunction has been viewed as a potential underlying mechanism of neurodegenerative disorders, possibly involved in the pathogenesis and progression of Alzheimer’s disease (AD). However, a relation between BBB dysfunction and dementia with Lewy bodies (DLB) has yet to be systematically investigated. Given the overlapping clinical features and neuropathology of AD and DLB, we sought to evaluate BBB permeability in the context of DLB and determine its association with plasma amyloid-β (Aβ) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For this prospective study, we examined healthy controls (n = 24, HC group) and patients diagnosed with AD (n = 29) or DLB (n = 20) between December 2020 and April 2022. Based on DCE-MRI studies, mean rates of contrast agent transfer from intra- to extravascular spaces (Ktrans) were calculated within regions of interest. Spearman’s correlation and multivariate linear regression were applied to analyze associations between Ktrans and specific clinical characteristics. In members of the DLB (vs HC) group, Ktrans values of cerebral cortex (p = 0.024), parietal lobe (p = 0.007), and occipital lobe (p = 0.014) were significantly higher; and Ktrans values of cerebral cortex (p = 0.041) and occipital lobe (p = 0.018) in the DLB group were significantly increased, relative to those of the AD group. All participants also showed increased Ktrans values of parietal ( $$upbeta$$ = 0.391; p = 0.001) and occipital ( $$upbeta$$ = 0.357; p = 0.002) lobes that were significantly associated with higher scores of the Clinical Dementia Rating, once adjusted for age and sex. Similarly, increased Ktrans values of cerebral cortex ( $$upbeta$$ = 0.285; p = 0.015), frontal lobe ( $$upbeta$$ = 0.237; p = 0.043), and parietal lobe ( $$upbeta$$ = 0.265; p = 0.024) were significantly linked to higher plasma Aβ1-42/Aβ1-40 ratios, after above adjustments. BBB leakage is a common feature of DLB and possibly is even more severe than in the setting of AD for certain regions of the brain. BBB leakage appears to correlate with plasma Aβ1-42/Aβ1-40 ratio and dementia severity.","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":"12 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}