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Keywords = cerebral pulsatility

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16 pages, 488 KB  
Study Protocol
Antidepressant and Related Neurobiological and Neurophysiological Effects of Add-On Transcranial Direct Current Stimulation in Major Depressive Disorder with Residual Symptoms: A Randomized, Double-Blind Clinical Trial Protocol
by Carmen Concerto, Fabrizio Bella, Cecilia Chiarenza, Alessandro Rodolico, Antonio Di Francesco, Alessia Ciancio, Stefania Lanzafame, Riccardo Spigarelli, Ludovico Mineo, Antonino Petralia, Raffaele Ferri, Massimo Libra, Rita Bella, Manuela Pennisi, Giuseppe Lanza and Maria Salvina Signorelli
Methods Protoc. 2025, 8(5), 117; https://doi.org/10.3390/mps8050117 - 2 Oct 2025
Viewed by 422
Abstract
Major depressive disorder (MDD) is a prevalent and disabling condition. Transcranial direct current stimulation (tDCS) may improve symptoms by modulating neuroplastic and inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial will recruit adult outpatients with MDD showing residual symptoms despite at least four weeks [...] Read more.
Major depressive disorder (MDD) is a prevalent and disabling condition. Transcranial direct current stimulation (tDCS) may improve symptoms by modulating neuroplastic and inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial will recruit adult outpatients with MDD showing residual symptoms despite at least four weeks of stable SSRI treatment. Participants will be randomized to active or sham add-on tDCS while continuing their antidepressant regimen. The intervention will consist of 15 sessions over 3 weeks, targeting the left dorsolateral prefrontal cortex (anode F3, cathode F4) at 2 mA for 30 min per session. The primary outcome is the reduction of depressive symptoms measured by the Hamilton Depression Rating Scale-17 (HDRS), with remission defined as HDRS-17 ≤ 7. Secondary outcomes include cognitive performance (attention, executive functioning, memory), serum biomarkers (BDNF, VEGF, NGF, NRG1, angiogenin, IGF1, IL-6, TNF-α), cortical excitability assessed by transcranial magnetic stimulation (motor threshold, silent period, intracortical inhibition/facilitation), and cerebral hemodynamics by transcranial Doppler sonography (blood flow velocity, pulsatility, resistivity). Assessments will occur at baseline, post-treatment, and 3- and 6-month follow-ups. This trial aims to evaluate the efficacy of adjunctive tDCS in MDD with residual symptoms and its biological correlates, bridging clinical improvement with electrophysiological and neurovascular mechanisms. Full article
(This article belongs to the Section Public Health Research)
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9 pages, 2275 KB  
Case Report
Ruling Out Internal Carotid Artery Agenesis in a Patient with Chronic Occlusion: A Case Report
by Merih Can Yilmaz and Keramettin Aydin
Clin. Transl. Neurosci. 2025, 9(4), 47; https://doi.org/10.3390/ctn9040047 - 2 Oct 2025
Viewed by 230
Abstract
Background/Objectives: This study presents a case of chronic internal carotid artery [ICA] occlusion initially misinterpreted as ICA agenesis on magnetic resonance angiography (MRA). The report underscores the importance of retrospective review of prior imaging, particularly computed tomography angiography [CTA], in establishing the [...] Read more.
Background/Objectives: This study presents a case of chronic internal carotid artery [ICA] occlusion initially misinterpreted as ICA agenesis on magnetic resonance angiography (MRA). The report underscores the importance of retrospective review of prior imaging, particularly computed tomography angiography [CTA], in establishing the correct diagnosis. Case Report: A 70-year-old man presented with persistent headache, pulsatile tinnitus, and intermittent dizziness. Neurological examination and laboratory results were unremarkable. Initial cranial MRA demonstrated absence of flow in the left ICA, raising suspicion of congenital agenesis. However, retrospective evaluation of a CTA performed nine years earlier revealed a well-formed left carotid canal without ICA opacification, confirming the diagnosis of chronic ICA occlusion. Results: Current imaging again showed lack of enhancement in the left ICA, with adequate cerebral perfusion supplied via the contralateral ICA and vertebrobasilar system. Recognition of the preserved carotid canal on earlier CTA clarified the diagnosis as chronic occlusion rather than agenesis. Although surgical or endovascular revascularization was recommended, the patient opted for conservative management. At three months of follow-up, symptoms had improved and clinical monitoring continues. Conclusions: This case underscores the importance of distinguishing ICA agenesis from chronic occlusion, particularly by evaluating the carotid canal on CT. The presence of a carotid canal strongly indicates prior patency of the ICA and supports a diagnosis of occlusion. Careful differentiation is critical to avoid misinterpretation and to guide appropriate clinical management. In addition, reviewing prior imaging can be valuable when current findings are inconclusive or potentially misleading. Since this is a single case report, these observations should be regarded as hypothesis-generating rather than definitive, and further studies are needed to validate their broader applicability. Full article
(This article belongs to the Section Neuroimaging)
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17 pages, 2173 KB  
Article
AI-Augmented Quantitative MRI Predicts Spontaneous Intracranial Hypotension
by Yi-Jhe Huang, Jyh-Wen Chai, Wen-Hsien Chen, Hung-Chieh Chen and Da-Chuan Cheng
Diagnostics 2025, 15(18), 2339; https://doi.org/10.3390/diagnostics15182339 - 15 Sep 2025
Viewed by 615
Abstract
Background/Objectives: Spontaneous intracranial hypotension (SIH), caused by spinal cerebrospinal fluid (CSF) leakage, commonly presents with orthostatic headache and CSF hypovolemia. While CSF dynamics in the cerebral aqueduct are well studied, alterations in spinal CSF flow remain less defined. We aimed to quantitatively [...] Read more.
Background/Objectives: Spontaneous intracranial hypotension (SIH), caused by spinal cerebrospinal fluid (CSF) leakage, commonly presents with orthostatic headache and CSF hypovolemia. While CSF dynamics in the cerebral aqueduct are well studied, alterations in spinal CSF flow remain less defined. We aimed to quantitatively assess spinal CSF flow at C2 using phase-contrast (PC) MRI enhanced by artificial intelligence (AI) and to evaluate its utility for diagnosing SIH and predicting responses to epidural blood patch (EBP). Methods: We enrolled 31 patients with MRI-confirmed SIH and 26 age- and sex-matched healthy volunteers (HVs). All participants underwent ECG-gated cine PC-MRI at the C2 level and whole-spine MR myelography. AI-based segmentation using YOLOv4 and a pulsatility-based algorithm was used to extract quantitative CSF flow metrics. Between-group comparisons were analyzed using Mann–Whitney U tests, and receiver operating characteristic (ROC) analysis was used to evaluate diagnostic and predictive performance. Results: Compared to HVs, SIH patients showed significantly reduced CSF flow parameters across all metrics, including upward/downward mean flow, peak flow, total flow per cycle, and absolute stroke volume (all p < 0.001). ROC analysis revealed excellent diagnostic accuracy for multiple parameters, particularly downward peak flow (AUC = 0.844) and summation of peak flow (AUC = 0.841). Importantly, baseline CSF flow metrics significantly distinguished patients who required one versus multiple epidural blood patches (EBPs) (all p < 0.001). ROC analysis demonstrated that several parameters achieved near-perfect to perfect accuracy in predicting EBP success, with AUCs up to 1.0 and 100% sensitivity/specificity. Conclusions: AI-enhanced PC-MRI enables the robust, quantitative evaluation of spinal CSF dynamics in SIH. These flow metrics not only differentiate SIH patients from healthy individuals but also predict response to EBP treatment with high accuracy. Quantitative CSF flow analysis may support both diagnosis and personalized treatment planning in SIH. Full article
(This article belongs to the Special Issue Brain MRI: Current Development and Applications)
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9 pages, 2729 KB  
Article
Vertebral Artery Sacrifice After Balloon Test Occlusion in Endovascular Repair of Subclavian Artery Aneurysm
by Carlo Coscarella, Rocco Giudice, Marta Minucci, Adelaide Borlizzi, Federico Francisco Pennetta, Bernardo Orellana Davila and Ciro Ferrer
J. Vasc. Dis. 2025, 4(3), 35; https://doi.org/10.3390/jvd4030035 - 11 Sep 2025
Viewed by 340
Abstract
Introduction: Isolated true subclavian artery aneurysm (SAA) is a rare form of peripheral arterial aneurysm that poses significant anatomical challenges to endovascular repair, especially in cases requiring planned vertebral artery (VA) sacrifice. The Balloon Occlusion Test (BOT) is a critical preoperative tool for [...] Read more.
Introduction: Isolated true subclavian artery aneurysm (SAA) is a rare form of peripheral arterial aneurysm that poses significant anatomical challenges to endovascular repair, especially in cases requiring planned vertebral artery (VA) sacrifice. The Balloon Occlusion Test (BOT) is a critical preoperative tool for evaluating collateral circulation before VA embolization. Case Report: A 74-year-old male was admitted with a pulsatile mass in the left supraclavicular fossa, and a 65 mm aneurysm of the intrathoracic segment of the left subclavian artery (LSA) involving critical arterial branches was diagnosed by computed tomography angiography. Due to his comorbidities, the patient was judged unfit for an open surgical repair of the aneurysm, and a two-stage endovascular subclavian aneurysm repair (EVSAR) was planned. The first step included embolization of the internal mammary artery and thyrocervical trunk, followed by BOT of the left VA, which confirmed an adequate perfusion of the posterior cerebral and cerebellar circulation that allowed safe VA embolization. The second step included zone 2 thoracic endograft placement (TEVAR) with LSA coverage and vascular plug occlusion of the proximal segment of the LSA and the axillary artery. Postoperative monitoring revealed no neurological deficit, and the patient was discharged home without complications. Follow-up imaging up to 24 months confirmed complete aneurysm exclusion and significant sac shrinkage. Conclusions: EVSAR with thoracic endograft and VA sacrifice, preceded by BOT, may be a safe and effective minimally invasive approach for the treatment of intrathoracic SAA. Full article
(This article belongs to the Section Peripheral Vascular Diseases)
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23 pages, 4599 KB  
Review
In Vitro Evaluation of Confounders in Brain Optical Monitoring: A Review
by Karina Awad-Pérez, Maria Roldan and Panicos A. Kyriacou
Sensors 2025, 25(18), 5654; https://doi.org/10.3390/s25185654 - 10 Sep 2025
Viewed by 585
Abstract
Optical brain monitoring techniques, including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), and photoplethysmography (PPG) have gained attention for their non-invasive, affordable, and portable nature. These methods offer real-time insights into cerebral parameters like cerebral blood flow (CBF), intracranial pressure (ICP), and oxygenation. [...] Read more.
Optical brain monitoring techniques, including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), and photoplethysmography (PPG) have gained attention for their non-invasive, affordable, and portable nature. These methods offer real-time insights into cerebral parameters like cerebral blood flow (CBF), intracranial pressure (ICP), and oxygenation. However, confounding factors like extracerebral layers, skin pigmentation, skull thickness, and brain-related pathologies may affect measurement accuracy. This review examines the potential impact of confounders, focusing on in vitro studies that use phantoms to simulate human head properties under controlled conditions. A systematic search identified six studies on extracerebral layers, two on skin pigmentation, two on skull thickness, and four on brain pathologies. While variation in phantom designs and optical devices limits comparability, findings suggest that the extracerebral layer and skull thickness influence measurement accuracy, and skin pigmentation introduces bias. Pathologies like oedema and haematomas affect the optical signal, though their influence on parameter estimation remains inconclusive. This review highlights limitations in current research and identifies areas for future investigation, including the need for improved brain phantoms capable of simulating pulsatile signals to assess the impact of confounders on PPG systems, given the growing interest in PPG-based cerebral monitoring. Addressing these challenges will improve the reliability of optical monitoring technologies. Full article
(This article belongs to the Collection Sensors for Globalized Healthy Living and Wellbeing)
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17 pages, 2624 KB  
Article
Cerebral Hemodynamics as a Diagnostic Bridge Between Mild Cognitive Impairment and Late-Life Depression: A Multimodal Approach Using Transcranial Doppler and MRI
by Sergiu-Florin Arnautu, Diana-Aurora Arnautu, Minodora Andor, Cristina Vacarescu, Dragos Cozma, Brenda-Cristina Bernad, Catalin Juratu, Adrian Tutelca and Catalin-Dragos Jianu
Life 2025, 15(8), 1246; https://doi.org/10.3390/life15081246 - 6 Aug 2025
Viewed by 737
Abstract
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler [...] Read more.
Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler (TCD) ultrasound parameters, cognitive performance, and depressive symptoms in older adults with mild cognitive impairment (MCI) and LLD. Importantly, we evaluated the integrative value of TCD-derived indices alongside MRI-confirmed white matter lesions (WMLs) and standardized neurocognitive and affective assessments. Methods: In this cross-sectional study, 96 older adults were enrolled including 78 cognitively unimpaired individuals and 18 with MCI. All participants underwent structured clinical, neuropsychological, and imaging evaluations including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15), MRI-based Fazekas scoring of WMLs, and TCD ultrasonography of the middle cerebral artery. Hemodynamic variables included mean blood flow velocity (MBFV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI). Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of MCI. Results: Participants with MCI showed significantly lower MBFV and EDV, and higher PI and RI (p < 0.05 for all) compared with cognitively unimpaired participants. In multivariate analysis, lower MBFV (OR = 0.64, p = 0.02) and EDV (OR = 0.70, p = 0.03), and higher PI (OR = 3.2, p < 0.01) and RI (OR = 1.9, p < 0.01) remained independently associated with MCI. ROC analysis revealed excellent discriminative performance for RI (AUC = 0.919) and MBFV (AUC = 0.879). Furthermore, PI correlated positively with depressive symptom severity, while RI was inversely related to the GDS-15 scores. Conclusions: Our findings underscore the diagnostic utility of TCD-derived hemodynamic parameters—particularly RI and MBFV—in identifying early vascular contributions to cognitive and affective dysfunction in older adults. The integration of TCD with MRI-confirmed WML assessment and standardized cognitive/mood measures represents a novel and clinically practical multi-modal approach for neurovascular profiling in aging populations. Full article
(This article belongs to the Special Issue Intracerebral Hemorrhage: Advances and Perspectives)
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15 pages, 1973 KB  
Article
VIVA Stent Preclinical Evaluation in Swine: A Novel Cerebral Venous Stent with a Unique Delivery System
by Yuval Ramot, Michal Steiner, Udi Vazana, Abraham Nyska and Anat Horev
J. Clin. Med. 2025, 14(13), 4721; https://doi.org/10.3390/jcm14134721 - 3 Jul 2025
Cited by 2 | Viewed by 886
Abstract
Background: Venous sinus stenting is a promising treatment for intracranial venous disorders, such as idiopathic intracranial hypertension and pulsatile tinnitus, associated with transverse sinus stenosis. The VIVA Stent System (VSS) is a novel self-expanding braided venous stent designed to navigate tortuous cerebral venous [...] Read more.
Background: Venous sinus stenting is a promising treatment for intracranial venous disorders, such as idiopathic intracranial hypertension and pulsatile tinnitus, associated with transverse sinus stenosis. The VIVA Stent System (VSS) is a novel self-expanding braided venous stent designed to navigate tortuous cerebral venous anatomy. This preclinical study assessed the safety, thrombogenicity, and performance of the VSS in a swine model. Methods: Fifteen swine underwent bilateral internal mammary vein stenting with either the VSS (n = 9) or the PRECISE® PRO RX stent (n = 6, reference). Fluoroscopy and thrombogenicity assessments were conducted on the day of stenting, clinical pathology analysis was carried out throughout the in-life phase, and CT Venography was performed before sacrifice. Animals were sacrificed at 30 ± 3 or 180 ± 11 days post-stenting for necropsy and histological evaluation. Results: Fluoroscopic angiography confirmed the successful VSS deployment with complete venous wall apposition and no vessel damage. The VSS achieved the highest scores on a four-point Likert scale for most performance parameters. No thrombus formation was observed on either delivery system. CT Venography confirmed vessel patency, no stent migration, and complete stent integrity. Histopathology showed a mild, expected foreign body reaction at 30 days, which resolved by 180 days, indicating normal healing progression. Both stents showed increased luminal diameter and decreased wall thickness at 180 days, suggesting vessel recovery. No adverse reactions were observed in non-target organs. Conclusions: The VSS exhibited favorable safety, procedural performance, and thromboresistance in a swine model, supporting its potential clinical use for treating transverse sinus stenosis and related conditions. Full article
(This article belongs to the Section Vascular Medicine)
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9 pages, 527 KB  
Brief Report
Correlation of Different Non-Invasive Neuromonitoring Tools Assessing Intracranial Hemodynamics
by Rossella Zangari, Luca D’Amelio, Elisa Gouvea Bogossian and Fabio Silvio Taccone
Brain Sci. 2025, 15(7), 710; https://doi.org/10.3390/brainsci15070710 - 30 Jun 2025
Cited by 1 | Viewed by 746
Abstract
Background: Intracranial pressure (ICP) monitoring is crucial in managing acute brain injury (ABI) to prevent secondary brain injury. While invasive techniques remain the gold standard, they can carry notable risks, such as infection and hemorrhage. Non-invasive techniques are increasingly used, but their inter-modality [...] Read more.
Background: Intracranial pressure (ICP) monitoring is crucial in managing acute brain injury (ABI) to prevent secondary brain injury. While invasive techniques remain the gold standard, they can carry notable risks, such as infection and hemorrhage. Non-invasive techniques are increasingly used, but their inter-modality correlation and concordance have not been systematically evaluated. This study aimed to assess the correlation and concordance among four commonly used non-invasive neuromonitoring tools in patients with ABI undergoing invasive ICP monitoring. Methods: This was a secondary analysis of prospectively collected data from 100 adult patients admitted to the intensive care unit with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) who underwent invasive ICP monitoring. Simultaneous assessments using optic nerve sheath diameter (ONSD), transcranial Doppler-derived pulsatility index (PI), estimated ICP (eICP), and the neurological pupil index (NPi) were performed. Correlation between modalities was assessed using Spearman’s correlation coefficient (ρ), and concordance was evaluated with Cohen’s kappa coefficient (k). Results: We found weak correlations between ONSD and PI (ρ = 0.29), ONSD and NPi (ρ = −0.33), and PI and NPi (ρ = −0.33); moderate correlations between ONSD and eICP (ρ = 0.54) and PI and eICP (ρ = 0.48); and a strong inverse correlation between eICP and NPi (ρ = −0.71; all p < 0.05). Concordance was generally low, with the highest agreement between PI and eICP (k = 0.69). Most other tool pairings showed poor-to-fair concordance (k ≤ 0.30). Conclusions: Non-invasive neuromonitoring tools show variable correlation and limited agreement, suggesting they are not interchangeable. Each modality captures different aspects of cerebral physiology, supporting the use of a multimodal approach to improve accuracy in ICP estimation. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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22 pages, 3830 KB  
Review
ABCC6 Involvement in Cerebral Small Vessel Disease: Potential Mechanisms and Associations
by Marialuisa Zedde and Rosario Pascarella
Genes 2025, 16(7), 728; https://doi.org/10.3390/genes16070728 - 23 Jun 2025
Cited by 1 | Viewed by 966
Abstract
ABCC6, a key regulator in ectopic calcification, plays a crucial role in mineralization through the modulation of extracellular purinergic pathways and production of inorganic pyrophosphate (PPi), which inhibits calcification. Inherited deficiencies in ABCC6 lead to pseudoxanthoma elasticum (PXE) and related conditions, characterized by [...] Read more.
ABCC6, a key regulator in ectopic calcification, plays a crucial role in mineralization through the modulation of extracellular purinergic pathways and production of inorganic pyrophosphate (PPi), which inhibits calcification. Inherited deficiencies in ABCC6 lead to pseudoxanthoma elasticum (PXE) and related conditions, characterized by calcification in various tissues, particularly affecting the skin, eyes, and cardiovascular system. Although PXE does not directly impact the nervous system, secondary neurological issues arise from cerebrovascular complications, increasing the risk of strokes linked to arterial blockages resembling atherosclerosis. This review investigates the connection between ABCC6 mutations and cerebral small vessel disease (SVD), expanding the understanding of PXE and related phenotypes. Mutations in ABCC6, identified as causing PXE, contribute to systemic metabolic dysfunction, with significant implications for cerebrovascular health. An association between ABCC6 mutations and cerebral SVD has been suggested in various studies, particularly in populations with distinct genetic backgrounds. Emerging evidence indicates that pathogenic mutations increase the risk of ischemic strokes, with both homozygous and heterozygous carriers showing susceptibility. Mechanistically, ABCC6 deficiency is implicated in dyslipidemia and atherosclerosis, further exacerbating cerebrovascular risks. Increased arterial pulsatility, linked to carotid siphon calcification, may also contribute to microvascular damage and subsequent brain injury. Understanding these mechanisms is vital for developing targeted diagnostic and therapeutic strategies for managing cerebrovascular risks in PXE patients. This review emphasizes the need for comprehensive genetic screening and the consideration of traditional vascular risk factors in patient management, highlighting the complex interplay between genetic mutations and environmental influences affecting cerebrovascular health. Future research should focus on longitudinal studies to elucidate the causal pathways linking arterial calcification, pulsatility, and brain damage in PXE. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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12 pages, 1837 KB  
Article
Non-Invasive Screening for Early Cognitive Impairment in Elderly Hyperuricaemic Men Using Transcranial Colour-Coded Duplex Sonography
by Zhirong Xu, Jiayi Ye, Han Wang, Jiemin Chen, Kailing Tan, Shilin Li and Shanshan Su
Diagnostics 2025, 15(12), 1519; https://doi.org/10.3390/diagnostics15121519 - 15 Jun 2025
Viewed by 579
Abstract
Objectives: Hyperuricaemia has been linked to cognitive decline, yet cerebral structural and haemodynamic changes in this population remain poorly defined. We evaluated transcranial colour-coded duplex (TCCD) sonography as a non-invasive screening tool for early mild cognitive impairment (MCI) in elderly hyperuricaemic men. Methods: [...] Read more.
Objectives: Hyperuricaemia has been linked to cognitive decline, yet cerebral structural and haemodynamic changes in this population remain poorly defined. We evaluated transcranial colour-coded duplex (TCCD) sonography as a non-invasive screening tool for early mild cognitive impairment (MCI) in elderly hyperuricaemic men. Methods: In this cross-sectional study, 195 men aged ≥ 60 years with hyperuricaemia were stratified by the Montreal Cognitive Assessment (MoCA) into HUA + MCI (MoCA < 26, n = 46) and HUA (MoCA ≥ 26, n = 149) groups. TCCD measured third-ventricle width (TVW) and peak systolic/end-diastolic velocities to calculate resistive (RI) and pulsatility (PI) indices in the middle (MCA) and posterior (PCA) cerebral arteries. Serum uric acid was recorded. Kernel density plots and receiver operating characteristic (ROC) curves assessed diagnostic performance. Results: The HUA + MCI group exhibited higher serum uric acid (508.5 ± 36.3 vs. 492.9 ± 44.0 µmol/L; p = 0.031), greater TVW (0.55 ± 0.11 vs. 0.51 ± 0.08 cm; p = 0.037), and elevated left PCA RI (0.69 ± 0.07 vs. 0.64 ± 0.06) and PI (1.05 ± 0.17 vs. 0.95 ± 0.12; both p < 0.001). ROC analysis identified left PCA PI as the most specific marker (AUC = 0.701; specificity 90.6%; sensitivity 45.7%). Kernel density plots confirmed distinct distributions of key parameters. Conclusions: TCCD-detected ventricular enlargement and raised PCA pulsatility accurately distinguish MCI among hyperuricaemic men. As a non-invasive, accessible technique with high specificity, TCCD may complement MRI and cognitive testing in early screening of at-risk populations. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Neurological Diseases)
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20 pages, 1713 KB  
Article
Stromal Cell-Derived Factor-1, P-Selectin, and Advanced Oxidation Protein Products with Mitochondrial Dysfunction Concurrently Impact Cerebral Vessels in Patients with Normoalbuminuric Diabetic Kidney Disease and Type 2 Diabetes Mellitus
by Ligia Petrica, Florica Gadalean, Adrian Vlad, Danina Mirela Muntean, Daliborca Vlad, Victor Dumitrascu, Flaviu Bob, Oana Milas, Anca Suteanu-Simulescu, Mihaela Glavan, Sorin Ursoniu, Lavinia Balint-Marcu, Maria Mogos-Stefan, Silvia Ienciu, Octavian Marius Cretu, Roxana Popescu, Cristina Gluhovschi, Lavinia Iancu and Dragos Catalin Jianu
Int. J. Mol. Sci. 2025, 26(10), 4481; https://doi.org/10.3390/ijms26104481 - 8 May 2025
Viewed by 1004
Abstract
Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential [...] Read more.
Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article
(This article belongs to the Special Issue Cell Biology in Diabetes and Diabetic Complications)
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10 pages, 1287 KB  
Brief Report
Silencing KRIT1 Partially Reverses the Effects of Disturbed Flow on the Endothelial Cell Transcriptome
by Amelia Meecham, Sara McCurdy, Eduardo Frias-Anaya, Wenqing Li, Helios Gallego-Gutierrez, Phu Nguyen, Yi-Shuan Li, Shu Chien, John Y.-J. Shyy, Mark H. Ginsberg and Miguel Alejandro Lopez-Ramirez
Int. J. Mol. Sci. 2025, 26(9), 4340; https://doi.org/10.3390/ijms26094340 - 2 May 2025
Cited by 1 | Viewed by 1324
Abstract
Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow shear stress are primarily mediated by the modulation of the following transcription factors: Krüppel-like factors 2 [...] Read more.
Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow shear stress are primarily mediated by the modulation of the following transcription factors: Krüppel-like factors 2 and 4 (KLF2 and KLF4). Notably, disturbed flow patterns, which are found in vascular areas predisposed to atherosclerosis, significantly reduce the endothelial expression of KLF2 and KLF4, resulting in changes in the transcriptome that exacerbate inflammation and thrombosis. The endothelial CCM (Cerebral Cavernous Malformation) complex, comprising KRIT1 (Krev1 interaction trapped gene 1), CCM2 (Malcavernin), and CCM3 (Programmed cell death protein 10), suppresses the expression of KLF2 and KLF4. Loss of function of the CCM complex has recently been suggested to protect from coronary atherosclerosis in humans. We thus hypothesized that the silencing of KRIT1, the central scaffold of the CCM complex, can normalize the atherogenic effects of disturbed flow on the human endothelial transcriptome. Bulk RNA sequencing (RNA-seq) was conducted on human umbilical vein endothelial cells (HUVECs) after the expression of KRIT1 was silenced using specific small interfering RNA (siRNA). The endothelial cells were exposed to three different conditions for 24 h, as follows: pulsatile shear stress (laminar flow), oscillatory shear stress (disturbed flow), and static conditions (no flow). We found that silencing the KRIT1 expression in HUVECs restored the expression of the transcription factors KLF2 and KLF4 under oscillatory shear stress. This treatment resulted in a transcriptomic profile similar to that of endothelial cells under pulsatile shear stress. These findings suggest that inhibition of the CCM complex in endothelium plays a vasoprotective role by reactivating a protective gene program to help endothelial cells resist disturbed blood flow. Targeting CCM genes can activate well-known vasoprotective gene programs that enhance endothelial resilience to inflammation, hypoxia, and angiogenesis under disturbed flow conditions, providing a novel pathway for preventing atherothrombosis. Full article
(This article belongs to the Section Molecular Biology)
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12 pages, 1505 KB  
Article
Cerebral Hemodynamic Alterations in Dialysis COVID-19 Survivors: A Transcranial Doppler Ultrasound Study on Intracranial Pressure Dynamics
by José Lapeña-Motilva, Daniel Fouz-Ruiz, Mariano Ruiz-Ortiz, Eduardo Sanpedro-Murillo, Sara Gómez-Enjuto, Inés Hernando-Jimenez, Aida Frias-González, Andrea Soledad Suso, Evangelina Merida-Herrero and Julián Benito-León
Kidney Dial. 2025, 5(2), 12; https://doi.org/10.3390/kidneydial5020012 - 3 Apr 2025
Viewed by 1000
Abstract
Background: We observed a COVID-19 survivor with a ventriculoperitoneal shunt who developed increased intracranial pressure during hemodialysis. We hypothesized that post-SARS-CoV-2 infection, patients may have altered cerebral perfusion pressure regulation in response to intracranial pressure changes. Methods: From April to July 2021, we [...] Read more.
Background: We observed a COVID-19 survivor with a ventriculoperitoneal shunt who developed increased intracranial pressure during hemodialysis. We hypothesized that post-SARS-CoV-2 infection, patients may have altered cerebral perfusion pressure regulation in response to intracranial pressure changes. Methods: From April to July 2021, we recruited dialysis patients with prior COVID-19 from two Madrid nephrology departments. We also recruited age- and sex-matched dialysis patients without prior SARS-CoV-2 infection. Transcranial Doppler ultrasound was used to measure the middle cerebral artery velocity before dialysis and 30, 60, and 90 min after the initiation of dialysis. Results: The final sample included 37 patients (16 post-COVID-19 and 21 without). The COVID-19 survivors showed a significant pulsatility index increase between 30 and 60 min compared to those without COVID-19. They also had lower heart rates. Conclusions: We propose two mechanisms: an increase in intracranial pressure or a decreased arterial elasticity. A lower heart rate was also observed in the COVID-19 survivors. This study highlights SARS-CoV-2’s multifaceted effects, including potential long-term vascular and cerebral repercussions. Full article
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15 pages, 2168 KB  
Article
The Prediction of Intrapartum Fetal Compromise According to the Expected Fetal Weight
by José Morales-Roselló, Alicia Martínez-Varea, Blanca Novillo-Del Álamo, Carmen Sánchez-Arco and Asma Khalil
J. Pers. Med. 2025, 15(4), 140; https://doi.org/10.3390/jpm15040140 - 1 Apr 2025
Cited by 1 | Viewed by 669
Abstract
Objectives: To assess the predictive accuracy of the expected fetal weight in the third trimester (ExFW3t), based on the estimated fetal weight (EFW) at mid-trimester ultrasound scan, for the prediction of intrapartum fetal compromise (IFC) (an abnormal intrapartum fetal heart rate or intrapartum [...] Read more.
Objectives: To assess the predictive accuracy of the expected fetal weight in the third trimester (ExFW3t), based on the estimated fetal weight (EFW) at mid-trimester ultrasound scan, for the prediction of intrapartum fetal compromise (IFC) (an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH requiring urgent cesarean section). Methods: This retrospective study included 777 singleton pregnancies that underwent a 20-week study and a 3t scan. The extrapolated EFW at 20 weeks to the 3t or ExFW3t was considered a proxy of the potential growth. The percentage difference with the actual 3t EFW (%ExFW3t) was compared with other ultrasonographic and clinical parameters—EFW centile (EFWc), middle cerebral artery pulsatility index (MCA PI) in multiples of the median (MoM), umbilical artery (UA) PI MoM, cerebroplacental ratio (CPR) MoM, and maternal height—for the prediction of IFC by means of the area under the curve (AUC) and Akaike Information Criteria (AIC). Results: Pregnancies with IFC presented higher values of UA PI MoM (1.19 vs. 1.09, p = 0.0460) and lower values of population and Intergrowth EFWc (45.9 vs. 28.9, p < 0.0001, 48.4 vs. 33.6, p = 0.0004), MCA PI MoM (0.97 vs. 0.81, p < 0.0001), CPR MoM (1.01 vs. 0.79, p < 0.0001), %ExFW3t (89.9% vs. 97.5%, p = 0.0003), and maternal height (160.2 vs. 162.9, p = 0.0083). Univariable analysis selected maternal height, EFWc, %ExFW3t, and UA PI MoM as significant parameters. However, %ExFW3t did not surpass the prediction ability of cerebral Doppler. Finally, multivariable analysis showed that the best models for the prediction of IFC resulted from the combination of cerebral Doppler (MCA PI MoM or CPR MoM), fetal weight (%ExFW3t or EFWc), and maternal height (AUC 0.75/0.76, AIC 345, p < 0.0001). Conclusions: Fetal weight-related parameters, including %ExFW3t, a proxy of the proportion of potential growth achieved in the 3t, were less effective than fetal cerebral Doppler for the prediction of IFC. The best performance was achieved by combining hemodynamic, ponderal, and clinical data. Full article
(This article belongs to the Section Personalized Therapy in Clinical Medicine)
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9 pages, 1286 KB  
Article
Assessment of Cerebral Hemodynamic Changes During Roll-Over Test in Healthy Pregnant Women and Those with Mild and Severe Preeclampsia
by Dániel T. Nagy, Béla Fülesdi, Bence Kozma, Dénes Páll, Szilárd Szatmári and Petronella Hupuczi
J. Clin. Med. 2025, 14(4), 1182; https://doi.org/10.3390/jcm14041182 - 11 Feb 2025
Cited by 3 | Viewed by 1465
Abstract
Background: Preeclampsia (PE) and eclampsia are characterized by changes in cerebral hemodynamics, which may result in serious and even life-threatening neurological complications. The aim of the present work was to compare cerebral hemodynamic changes during the roll-over test in women with mild and [...] Read more.
Background: Preeclampsia (PE) and eclampsia are characterized by changes in cerebral hemodynamics, which may result in serious and even life-threatening neurological complications. The aim of the present work was to compare cerebral hemodynamic changes during the roll-over test in women with mild and severe PE. Patients and methods: Healthy pregnant and PE women in their third trimester were studied. Transcranial Doppler (TCD) measurements of the right middle cerebral artery (MCA) were performed in the left lateral position and 5 min after turning to the supine position (roll-over test = ROT). Besides cerebral blood flow measurements, the blood pressure was measured in the right arm using a standard mercury sphygmomanometer. An independent gynecologist categorized the preeclamptic patients into mild and severe groups based on the clinical and laboratory results. The TCD assessors were unaware of the patient grouping while performing the TCD and blood pressure measurements. Results: A total of 21 healthy pregnant females (mean age: 26.1 ± 5.1 yrs), 11 females with mild PE (28.2 ± 6.8 yrs), and 18 females with severe PE (29 ± 7.4 yrs) were studied. A significant increase in the mean arterial pressure was observed in all of the groups during the roll-over test: healthy pregnant patients: from 106.3 ± 16.3 to 113.8 ± 15.9 mmHg; patients with mild PE: from 100 ± 11.2 to 110 ± 8.7 mmHg; and patients with severe PE: from 106.3 ± 16.3 to 113.8 ± 15.8 mmHg. The MCA mean blood flow velocities in the left lateral position were significantly lower in the control patients than in those with PE: MCAV control: 71.2 ± 12.7 cm/s; mild PE: 78.2 ± 19.4 cm/s; and severe PE: 96 ± 15.6 cm/s, p < 0.001. Turning to the supine position resulted in a decrease in the MCAV in all of the groups, but the differences between the groups remained unchanged: controls: 69.5 ± 9.1 cm/s; mild PE: 75.7 ± 17.5 cm/s; and severe PE: 85.7 ± 18.4 cm/s, respectively, p = 0.014. A slight but statistically insignificant increase in the pulsatility index was observed in all of the groups. Conclusions: This is the first study comparing cerebral hemodynamic changes in healthy pregnant females and in those with mild and severe PE during a roll-over test. Changing the posture did not result in changes in the cerebral blood flow velocities in the healthy and preeclamptic pregnant patients. Our results indicate that static cerebral autoregulation is preserved both in the mild and severe preeclamptic patients. Full article
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