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58 pages, 1238 KiB  
Review
The Collapse of Brain Clearance: Glymphatic-Venous Failure, Aquaporin-4 Breakdown, and AI-Empowered Precision Neurotherapeutics in Intracranial Hypertension
by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc
Int. J. Mol. Sci. 2025, 26(15), 7223; https://doi.org/10.3390/ijms26157223 - 25 Jul 2025
Viewed by 355
Abstract
Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is [...] Read more.
Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2025)
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8 pages, 206 KiB  
Comment
Gender-Dependent Modulation of Alzheimer’s Disease by Brain Ischemia. Comment on Lohkamp et al. Sex-Specific Adaptations in Alzheimer’s Disease and Ischemic Stroke: A Longitudinal Study in Male and Female APPswe/PS1dE9 Mice. Life 2025, 15, 333
by Ryszard Pluta
Life 2025, 15(7), 1146; https://doi.org/10.3390/life15071146 - 21 Jul 2025
Viewed by 279
Abstract
This comment focuses on the contribution of experimental brain ischemia to the overwhelming incidence of Alzheimer’s disease in women as presented by Lohkamp et al. in Life 2025, 15, 333. The authors showed that in Alzheimer’s disease and ischemic stroke there are sex-dependent [...] Read more.
This comment focuses on the contribution of experimental brain ischemia to the overwhelming incidence of Alzheimer’s disease in women as presented by Lohkamp et al. in Life 2025, 15, 333. The authors showed that in Alzheimer’s disease and ischemic stroke there are sex-dependent adaptations in the form of cross-links and vice versa. It was emphasized that the high longevity of women in itself does not explain the mechanisms underlying the biological differences between the sexes causing a female predominance in the development of Alzheimer’s disease. Differences were demonstrated between males and females: female APP/PS1 mice had greater amyloid deposition, hyperactivity, lower body weight, and reduced cerebral blood flow, as well as less neuroinflammation, which the authors suggest may have potential neuroprotection. It should be noted that some of the information presented in the article by Lohkamp et al. raises more questions than answers. Therefore, future studies should consider, for example, studies using single-cell technologies that can provide insight into the timing and sequence of cellular dysfunctions across sexes and analyze the continuity of changes over time, starting from short-term observations of a few days and ending with long-term observations of a year or more, to assess the continuity and differentiation of changes. Full article
(This article belongs to the Section Medical Research)
20 pages, 7186 KiB  
Article
A Novel Approach to Non-Invasive Intracranial Pressure Wave Monitoring: A Pilot Healthy Brain Study
by Andrius Karaliunas, Laimonas Bartusis, Solventa Krakauskaite, Edvinas Chaleckas, Mantas Deimantavicius, Yasin Hamarat, Vytautas Petkus, Toma Stulge, Vytenis Ratkunas, Guven Celikkaya, Ingrida Januleviciene and Arminas Ragauskas
Sensors 2025, 25(13), 4042; https://doi.org/10.3390/s25134042 - 28 Jun 2025
Viewed by 585
Abstract
Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive [...] Read more.
Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive alternatives. This pilot study investigates a novel non-invasive method for monitoring ICP pulse waves through closed eyelids, using a specially designed, liquid-filled, fully passive sensor system named ‘Archimedes 02’. To our knowledge, this is the first technological approach that enables the non-invasive monitoring of ICP pulse waveforms via closed eyelids. This study involved 10 healthy volunteers, aged 26–39 years, who underwent resting-state non-invasive ICP pulse wave monitoring sessions using the ‘Archimedes 02’ device while in the supine position. The recorded signals were processed to extract pulse waves and evaluate their morphological characteristics. The results indicated successful detection of pressure pulse waves, showing the expected three peaks (P1, P2, and P3) in all subjects. The calculated P2/P1 ratios were 0.762 (SD = ±0.229) for the left eye and 0.808 (SD = ±0.310) for the right eye, suggesting normal intracranial compliance across the cohort, despite variations observed in some individuals. Physiological tests—the Valsalva maneuver and the Queckenstedt test, both performed in the supine position—induced statistically significant increases in the P2/P1 and P3/P1 ratios, supporting the notion that non-invasively recorded pressure pulse waves, measured through closed eyelids, reflect intracranial volume and pressure dynamics. Additionally, a transient hypoemic/hyperemic response test performed in the upright position induced signal changes in pressure recordings from the ‘Archimedes 02’ sensor that were consistent with intact cerebral blood flow autoregulation, aligning with established physiological principles. These findings indicate that ICP pulse waves and their dynamic changes can be monitored non-invasively through closed eyelids, offering a potential method for brain monitoring in patients for whom invasive procedures are not feasible. Full article
(This article belongs to the Special Issue Integrated Sensor Systems for Medical Applications)
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17 pages, 5186 KiB  
Article
Abnormal Cerebral Perfusion and Functional Connectivity in Women with Overactive Bladder
by Shichun Chen, Zongpai Zhang, Yakun Zhang, Kenneth Wengler, Steven Weissbart, Weiying Dai, Xiang He and Justina Tam
Brain Sci. 2025, 15(7), 689; https://doi.org/10.3390/brainsci15070689 - 27 Jun 2025
Viewed by 426
Abstract
Background: Overactive bladder (OAB) has been linked to abnormal cerebral blood flow (CBF) and functional connectivity (FC). However, findings related to CBF and FC changes in OAB remain inconsistent across the literature. Methods: This feasibility study employed arterial spin labeling (ASL) to investigate [...] Read more.
Background: Overactive bladder (OAB) has been linked to abnormal cerebral blood flow (CBF) and functional connectivity (FC). However, findings related to CBF and FC changes in OAB remain inconsistent across the literature. Methods: This feasibility study employed arterial spin labeling (ASL) to investigate abnormal CBF and posterior cingulate cortex (PCC) FC in individuals with OAB, both at rest and during bladder filling. ASL images were collected from twenty-two female participants (twelve with OAB and ten healthy controls) at bladder filling volumes of 0, 50, 100, 200, 350, and 500 mL. For OAB participants, scans were obtained both at baseline and following a single-session treatment. ASL images were categorized into low-urge and high-urge conditions based on participants’ subjective urge rating during bladder filling. A flexible factorial design was implemented with three factors: subject, group (control, OAB at baseline, and OAB posttreatment), and urge state (low vs. high). Results: Compared to controls, OAB participants exhibited significant decreases in ΔCBF (high urge minus low urge) in the medial prefrontal cortex and increases in ΔCBF in the supramarginal region. Additionally, ΔPCC FC with the insula was reduced in OAB participants. Posttreatment, OAB participants showed increased ΔPCC FC with the postcentral and parietal (PocP), regions associated with the sensorimotor network. Notably, changes in ΔPCC-PocP FC were associated with improvements in OAB symptoms. Conclusions: These findings support the feasibility of using ASL to probe dysfunctional brain–bladder control mechanisms and treatment-related changes in OAB participants, highlighting the involvement of sensory processing and attention regulation in this condition. Full article
(This article belongs to the Special Issue Application of MRI in Brain Diseases)
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22 pages, 1759 KiB  
Article
The Impact of Cocoa Flavanols in Modulating Resting Cerebral Blood Flow During Prolonged Sitting in Healthy Young and Older Adults
by Alessio Daniele, Samuel J. E. Lucas and Catarina Rendeiro
Nutrients 2025, 17(13), 2099; https://doi.org/10.3390/nu17132099 - 24 Jun 2025
Viewed by 1272
Abstract
Background: Sitting is highly prevalent among young and older adults and can transiently reduce cerebral blood flow. Dietary flavanols confer benefits to the peripheral vasculature and may be effective at counteracting the impact of sitting in the cerebrovasculature. The aim of this study [...] Read more.
Background: Sitting is highly prevalent among young and older adults and can transiently reduce cerebral blood flow. Dietary flavanols confer benefits to the peripheral vasculature and may be effective at counteracting the impact of sitting in the cerebrovasculature. The aim of this study was to investigate whether the acute ingestion of flavanols prior to sitting improves common carotid artery (CCA) blood flow/shear rate (BF/SR) in young and older individuals. Methods: Two acute randomized, double-blinded, cross-over, placebo-controlled studies were conducted in 40 healthy young males (high-fit: 22.2 ± 2.9 yr., low-fit: 23.2 ± 4.1 yr., N = 20 per group) and 20 healthy older adults (72.4 ± 5.0 yr.). Participants consumed either a high- (695 mg) or low-flavanol (5.6 mg) cocoa beverage just before a 2 h sitting bout. Resting CCA retrograde/anterograde BF and SR, as well as arterial diameter, were assessed before and after the intervention. Results: Sitting reduced anterograde BF and/or SR in young and older individuals (p < 0.001) but only resulted in increases in retrograde BF (p = 0.021) and SR (p = 0.022) in the older group. Flavanols did not affect anterograde BF/SR in either group (p > 0.05) but mitigated (non-significant interaction: p = 0.053) sitting-induced increases in retrograde BF/SR in older individuals, with retrograde BF (p = 0.028) and SR (p = 0.033) increasing significantly only after intake of the low-flavanol beverage. No changes in arterial diameter were detected. Conclusions: This suggests that flavanols may have the potential to attenuate the detrimental sitting-induced increases in retrograde BF and SR in older adults, although larger well-powered studies are required to confirm this. Full article
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10 pages, 714 KiB  
Article
Regional Cerebral Blood Flow Increase After Transcatheter Aortic Valve Replacement Is Related to Cardiac Output but Is Not Associated with Delirium: An Observational Cohort Study Using Transcranial Indocyanine Green Dye Dilution Technique
by Maximilian Oremek, Paul Nowotny, Sebastian Zimmer, Atsushi Sugiura, Leonie Weinhold, Juerg Froehlich, Martin Soehle, André Diedrich and Marcus Thudium
J. Clin. Med. 2025, 14(12), 4317; https://doi.org/10.3390/jcm14124317 - 17 Jun 2025
Viewed by 349
Abstract
Background: Despite the success of transcatheter aortic valve repair (TAVR) over the past years, its impact on global and cerebral hemodynamics remains largely unexplored. Changes in cerebral blood flow may be associated with delirium, which may occur in 26 to 29% of cases. [...] Read more.
Background: Despite the success of transcatheter aortic valve repair (TAVR) over the past years, its impact on global and cerebral hemodynamics remains largely unexplored. Changes in cerebral blood flow may be associated with delirium, which may occur in 26 to 29% of cases. We aimed to examine the relationships between global hemodynamic parameters and cerebral parameters in patients who underwent TAVR and their impact on postinterventional delirium. Methods: Patients scheduled for TAVR were enrolled after obtaining written informed consent. Patients received light sedation according to standard procedures. Cerebral blood flow (CBF) was measured with a noninvasive near-infrared spectroscopy-based method using intravenous indocyanine green injection. CBF measurements were taken at the beginning of the TAVR procedure and after the valve was in place. Patients were screened for delirium using CAM-ICU and NuDESC tests before and after intervention. Results: A total of 52 of 60 patients remained for analysis. Thirteen patients (25%) developed delirium. Mean arterial pressure (MAP) remained unchanged, while cardiac output increased after TAVR by 44%. CBF also increased after TAVR. No significant difference was observed in CBF changes between the groups with and without delirium. A linear mixed model analysis revealed a linear relationship between CO and CBF but not between MAP and CBF. In an exploratory analysis, decreased cerebral oxygenation and increased deoxygenated hemoglobin, as measured by NIRS after TAVR, were associated with delirium. Conclusions: The results confirm that CO is an independent factor in CBF, while CBF changes per se are not linked to delirium. However, we found a mismatch between CBF and regional cerebral parameters, which may reflect cerebral metabolism and its relation to the development of delirium. This remains to be confirmed by further studies. Full article
(This article belongs to the Section Cardiovascular Medicine)
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23 pages, 4529 KiB  
Article
The Relevance of Optical Coherence Tomography Angiography in Screening and Monitoring Hypertensive Patients with Carotid Artery Stenosis
by Irina Cristina Barca, Vasile Potop and Stefan Sorin Arama
Diagnostics 2025, 15(11), 1393; https://doi.org/10.3390/diagnostics15111393 - 30 May 2025
Viewed by 451
Abstract
Background: Our study evaluated the correlation between internal carotid artery stenosis (ICAS) and retinal microvascular changes in patients with hypertensive retinopathy, dyslipidemia and ICAS. We analyzed vascular measurements provided by optical coherence tomography angiography (OCTA) and carotid Doppler ultrasonography (US) and linked [...] Read more.
Background: Our study evaluated the correlation between internal carotid artery stenosis (ICAS) and retinal microvascular changes in patients with hypertensive retinopathy, dyslipidemia and ICAS. We analyzed vascular measurements provided by optical coherence tomography angiography (OCTA) and carotid Doppler ultrasonography (US) and linked OCTA parameters with carotid artery US measurements on the same side. Statistical differences in OCTA analysis among three groups (no stenosis, mild stenosis and moderate stenosis) were evaluated and correlated with carotid Doppler parameters. Our study aimed to evaluate whether OCTA can be proposed as a screening method in patients diagnosed with mild and moderate ICAS in order to improve the early detection of carotid changes, thus potentially reducing the rate of cardiovascular and cerebral complications of ICAS. Methods: We conducted a study on hypertensive patients with ICAS using six OCTA parameters in the analysis of the retinal vasculature and carotid Doppler US velocities of three carotid arteries and the vertebral artery (VA). Kruskal–Wallis and Dunn’s post hoc tests were used to determine whether there were statistically significant differences between the normal, mild and moderate stenosis groups. Spearman and Pearson correlation were used to obtain correlations among OCTA parameters such as the foveal avascular zone (FAZ), non-flow area (NFA), vascular flow area (VFA) and blood flow velocity on carotid Doppler US. Results: In the final analysis, 49 patients were included and 3 groups of stenosis were obtained, comprising 21 subjects with no stenosis, 19 with mild stenosis and 9 with moderate stenosis. Right eye and left eye groups were formed. In the right eye group with right ICAS, we found statistically significant results for FAZ circularity when comparing the normal stenosis group to the mild stenosis group (p = 0.025) and the mild stenosis group to the moderate stenosis group (p = 0.006). Statistically significant results were also observed for NFA when comparing the normal stenosis group to the moderate stenosis group (p = 0.004) and the mild stenosis group to the moderate stenosis group (p = 0.011). When comparing the FAZ area (p = 0.016) and VFA (p = 0.037) for the normal and moderate groups, statistically significant values were obtained. When comparing the normal and moderate stenosis groups with regard to the left eye, we found statistically significant results for VFA (p = 0.041), NFA (p = 0.045) and VFA (p = 0.029). When comparing the mild and moderate carotid artery stenosis groups, we obtained statistically significant results for NFA (p = 0.001), FAZ area (p = 0.007) and VFA (p = 0.013). In the right eye group, correlations between internal carotid artery (ICA) peak systolic velocity (PSV) and VFA (rho = −0.286), ICA end-diastolic velocity (EDV) and NFA (r = 0.365), external carotid artery (ECA) PSV and VFA (r = −0.288; rho = −0.317), common carotid artery (CCA) PSV and NFA (rho = −0.345), CCA EDV and NFA (rho = −0.292) and VA PSV and VFA (r = −0.327; rho = −0.379) were found. When analyzing OCTA parameters, we found statistically significant results for NFA and VFA (r = −0.374; rho = −0.288). Correlations were also found in the left eye group between ICA PSV and NFA (r = −0.351; rho = −0.313), ICA EDV and VFA (r = −0.421; rho = −0.314), ECA PSV and NFA (r = −0.412; rho = −0.457), CCA PSV and NFA (p = −0.288; rho = −0.339), and CCA EDV and NFA (r = −0.404; rho = −0.417). Conclusions: Our study found correlations between carotid Doppler velocities and OCTA vascular flow parameters; thus, OCTA may be used as a tool for monitoring the microvascular changes associated with carotid stenosis. OCTA can provide insights concerning the overall vascular condition of the patient, since it provides subjective data on vessel density and flow; therefore, by monitoring hypertensive patients with both OCTA and carotid Doppler US, we may be able to increase efficiency in screening and diagnosing patients with IACS. Full article
(This article belongs to the Special Issue Advances in Optical Coherence Tomography in 2025)
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10 pages, 1287 KiB  
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 841
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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21 pages, 4993 KiB  
Article
The Impact of Distance and Altitude on Railway Environmental Noise Based on Cerebral Oxygenated Hemoglobin Saturation
by Min-kyeong Kim and Duckshin Park
Brain Sci. 2025, 15(5), 439; https://doi.org/10.3390/brainsci15050439 - 24 Apr 2025
Viewed by 543
Abstract
Railways are considered an environmentally sustainable mode of transportation but can pose significant environmental challenges due to their operation and associated activities. Among these, noise generation is a persistent source of public complaints. In Korea, a maximum distance of 100 m from buildings [...] Read more.
Railways are considered an environmentally sustainable mode of transportation but can pose significant environmental challenges due to their operation and associated activities. Among these, noise generation is a persistent source of public complaints. In Korea, a maximum distance of 100 m from buildings has been proposed for new railway developments in residential areas, although this guideline lacks a solid foundation based on experimental evidence. Noise barriers are often installed as a mitigation measure; however, there is no standardized guideline for their height in relation to their effectiveness at varying distances. The distances and altitudes set in this study took into account accessibility and the height of noise barriers on actual railway sites. In particular, we examined the effects of altitude above and distance from a railway site under the assumption that the prefrontal cortex would be physiologically affected by noise exposure. In this study, we conducted the first analysis in Korea of cerebral blood flow changes in response to noise, to assess quantitatively the stress effects caused by railway environmental noise at varying distances from, and altitudes above, a railway. Using functional near-infrared spectroscopy (fNIRS), we measured prefrontal cortex activation in 10 adult males (average age: 33.2 years). Brain activation was evaluated under different distances from (40 and 100 m) and altitudes above (1st and 4th floors of a building) a railway through a paired-sample t-test analysis. Discomfort was felt at relatively close distances to the railway, and there were no differences in perceived discomfort between the examined floors. Brain activation due to environmental noise was highest in channel 43 (left DLPFC) for altitude (floor) and in channel 37 (left FPC) for distance. Significant differences in activation were observed in the corresponding Brodmann areas, varying based on altitude and distance (p < 0.05). These results provide valuable scientific data for the preliminary design phase of new railway developments, particularly with regard to determining appropriate residential distance and noise barrier specifications, to enhance comfort of nearby residents. Furthermore, they may contribute to the improvement of quality of life by reducing stress caused by railway environmental noise. Full article
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21 pages, 1808 KiB  
Review
Neuromodulation of Cerebral Blood Flow: A Physiological Mechanism and Methodological Review of Neurovascular Coupling
by Jiawen Zhong, Gen Li, Zexiang Lv, Jingbo Chen, Chunyan Wang, Ansheng Shao, Zhiwei Gong, Junjie Wang, Siqiao Liu, Jun Luo, Shuping Yang, Sibei Wu, Lin Ning, Zhinong Wang, Jiahao Li and Yu Wu
Bioengineering 2025, 12(5), 442; https://doi.org/10.3390/bioengineering12050442 - 23 Apr 2025
Cited by 1 | Viewed by 2475
Abstract
Neurovascular coupling (NVC) refers to the dynamic regulation of cerebral blood flow via neuronal activity, a mechanism crucial for maintaining normal brain function. This review elucidates the intricate physiological mechanisms underlying NVC, emphasizing the coordinated roles of neurons, glial cells, and vascular cells [...] Read more.
Neurovascular coupling (NVC) refers to the dynamic regulation of cerebral blood flow via neuronal activity, a mechanism crucial for maintaining normal brain function. This review elucidates the intricate physiological mechanisms underlying NVC, emphasizing the coordinated roles of neurons, glial cells, and vascular cells in mediating activity-induced changes in blood flow. We examine how NVC is impaired in neurological disorders such as Alzheimer’s disease and stroke, where the dysfunction of this coupling contributes to neurodegeneration and neurological deficits. A broad range of techniques for assessing NVC is discussed—encompassing the established modalities like transcranial Doppler, near-infrared spectroscopy, and functional magnetic resonance imaging (fMRI), as well as emerging technologies such as functional ultrasound imaging and miniaturized endoscopy that enable high-resolution monitoring in deep brain regions. We also highlight the computational modeling approaches for simulating NVC dynamics and identify the novel biomarkers of NVC dysfunction with potential utility in early diagnosis. Finally, emerging translational applications—including neuromodulation techniques and targeted pharmacological interventions—are explored as means to restore normal neurovascular function. These advancements underscore the clinical significance of NVC research, paving the way for improved diagnostic tools and therapeutic strategies in neurological disorders. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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18 pages, 5527 KiB  
Article
Bilateral Cerebral Hypoperfusion in Asymptomatic Unilateral Carotid Artery Stenosis: An Arterial Spin Labeling MRI Study
by Nikola Dacic, Srdjan Stosic, Olivera Nikolic, Zoran D. Jelicic, Aleksandra Dj Ilic, Mirna N. Radovic and Jelena Ostojic
Medicina 2025, 61(5), 771; https://doi.org/10.3390/medicina61050771 - 22 Apr 2025
Viewed by 635
Abstract
Background and Objectives: Carotid artery stenosis is a significant risk factor for ischemic stroke due to impaired cerebral blood flow (CBF). Even asymptomatic unilateral stenosis can induce subclinical cerebrovascular changes, potentially affecting both hemispheres through collateral circulation. This study aimed to systematically [...] Read more.
Background and Objectives: Carotid artery stenosis is a significant risk factor for ischemic stroke due to impaired cerebral blood flow (CBF). Even asymptomatic unilateral stenosis can induce subclinical cerebrovascular changes, potentially affecting both hemispheres through collateral circulation. This study aimed to systematically assess cerebral perfusion in asymptomatic individuals with unilateral carotid artery stenosis by comparing ipsilateral and contralateral hemispheres with healthy controls, challenging the assumption that the contralateral hemisphere remains unaffected. Materials and Methods: This cross-sectional study included 114 participants, comprising 54 asymptomatic individuals (mean age 65.5) with significant unilateral carotid stenosis and 60 age-matched controls (mean age 64.8). Cerebral perfusion was assessed using 1.5T Magnetic Resonance Imaging (MRI) with pseudo-continuous arterial spin labeling (pCASL). CBF was measured bilaterally in four predefined middle cerebral artery (MCA) regions: precentral gyrus, lentiform nucleus, insular cortex, and temporal cortex. Statistical analyses included multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), paired t-tests, and discriminant analysis (DA). Results: Significant bilateral reductions in CBF were observed in individuals with carotid stenosis compared to controls (MANOVA and ANOVA, p < 0.001). The greatest perfusion deficit was in the ipsilateral insular cortex (49.88 ± 10.83 mL/100 g/min), followed by intermediate contralateral perfusion (51.49 ± 8.86 mL/100 g/min) and higher control values (58.78 ± 10.44 mL/100 g/min). DA indicated the insular cortex as the region with the highest discriminative contribution (64.7%). Conclusions: Unilateral carotid artery stenosis in asymptomatic individuals is associated with significant bilateral cerebral hypoperfusion, suggesting widespread hemodynamic effects. Pronounced perfusion deficits in the insular cortex underline its vulnerability. The observed contralateral perfusion reductions challenge the traditional use of the contralateral hemisphere as a reference standard, underscoring the need for comprehensive perfusion assessment in carotid artery disease. Full article
(This article belongs to the Section Neurology)
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19 pages, 5040 KiB  
Article
Integrative Proteomic and Phosphoproteomic Profiling Reveals Molecular Mechanisms of Hypoxic Adaptation in Brandt’s Voles (Lasiopodomys brandtii) Brain Tissue
by Panqin Wang, Yongyan Liu, Yimeng Du, Yiwen Gao, Tian Shao, Weifeng Guo, Zhenlong Wang and Han Cheng
Cells 2025, 14(7), 527; https://doi.org/10.3390/cells14070527 - 1 Apr 2025
Viewed by 554
Abstract
Rapid ascent to high altitudes by unacclimatized individuals significantly increases the risk of brain damage, given the brain’s heightened sensitivity to hypoxic conditions. Investigating hypoxia-tolerant animals can provide insights into adaptive mechanisms and guide prevention and treatment of hypoxic-ischemic brain injury. In this [...] Read more.
Rapid ascent to high altitudes by unacclimatized individuals significantly increases the risk of brain damage, given the brain’s heightened sensitivity to hypoxic conditions. Investigating hypoxia-tolerant animals can provide insights into adaptive mechanisms and guide prevention and treatment of hypoxic-ischemic brain injury. In this study, we exposed Brandt’s voles to simulated altitudes (100 m, 3000 m, 5000 m, and 7000 m) for 24 h and performed quantitative proteomic and phosphoproteomic analyses of brain tissue. A total of 3990 proteins and 9125 phosphorylation sites (phospho-sites) were quantified. Differentially expressed (DE) analysis revealed that while protein abundance changes were relatively modest, phosphorylation levels exhibited substantial alterations, suggesting that Brandt’s voles rapidly regulate protein structure and function through phosphorylation to maintain cellular homeostasis under acute hypoxia. Clustering analysis showed that most co-expressed proteins exhibited non-monotonic responses with increasing altitude, which were enriched in pathways related to cytokine secretion regulation and glutathione metabolism, contributing to reduced inflammation and oxidative stress. In contrast, most co-expressed phospho-sites showed monotonic changes, with phospho-proteins enriched in glycolysis and vascular smooth muscle contraction regulation. Kinase activity prediction identified nine hypoxia-responsive kinases, four of which belonging to the CAMK family. Immunoblot validated that the changes in CAMK2A activity were consistent with predictions, suggesting that CAMK may play a crucial role in hypoxic response. In conclusion, this work discovered that Brandt’s voles may cope with hypoxia through three key strategies: (1) vascular regulation to enhance cerebral blood flow, (2) glycolytic activation to increase energy production, and (3) activation of neuroprotective mechanisms. Full article
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14 pages, 4441 KiB  
Article
Towards an Automatic Recognition of Artifacts and Features in Plethysmographic Traces
by Alessandro Breccia, Marco Chiloiro, Riccardo Lui, Konstantinos Panagiotakis, Gianfranco Paternò, Antonino Proto, Angelo Taibi and Alberto Zucchetta
Appl. Sci. 2025, 15(6), 3187; https://doi.org/10.3390/app15063187 - 14 Mar 2025
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Abstract
A plethysmograph is a device that quantitatively assesses volumetric variations in an organ or the entire body, typically resulting from fluctuations in blood flow. In this study, a strain-gauge sensor that measures changes in the volume of the neck was used to detect [...] Read more.
A plethysmograph is a device that quantitatively assesses volumetric variations in an organ or the entire body, typically resulting from fluctuations in blood flow. In this study, a strain-gauge sensor that measures changes in the volume of the neck was used to detect the the cerebral venous outflow in the internal jugular veins. The resulting electronic signal was susceptible to several external factors, complicating the identification of relevant features. A reliable analysis of the waveform, without the need for a manual intervention to analyze the data, is of paramount importance to provide real-time analysis of the vital parameters of the patient. In this work, we demonstrate that specifically designed neural networks can detect artifacts in plethysmographic traces and identify the most important features in the signal with reasonable accuracy, eliminating the need to perform these tasks manually for each patient. Full article
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17 pages, 7099 KiB  
Article
Optimization of Illuminance and Color-Temperature Conditions for Railway Passengers’ Comfort Based on Oxygenated Hemoglobin Saturation in the Brain
by Minkyeong Kim, Jooyeon Lee, Yonghee Lee and Duckshin Park
Toxics 2025, 13(3), 212; https://doi.org/10.3390/toxics13030212 - 14 Mar 2025
Cited by 1 | Viewed by 648
Abstract
Railway travel is an eco-friendly means of transportation, and passengers are spending increasing amounts of time on trains while engaging in various activities. As a major factor affecting railway passengers’ comfort, we investigated the effects of lighting. Korean train cars are required to [...] Read more.
Railway travel is an eco-friendly means of transportation, and passengers are spending increasing amounts of time on trains while engaging in various activities. As a major factor affecting railway passengers’ comfort, we investigated the effects of lighting. Korean train cars are required to have two rows of light-emitting diode lights with a minimum illuminance of 500 lx, so we examined changes in cerebral blood flow under various illuminance conditions around this threshold value. We used functional near-infrared spectroscopy to measure prefrontal cortex activation in 29 college students under illuminance values of 300, 500, and 800 lx and color-temperature values of 2700 K (bulb color), 4000 K (white color), and 5500 K (blue color). Mean brain activity values were compared using analysis of variance. Of the 48 channels, significant interaction effects between color and illuminance on brain activation responses were observed for channel 38, as well as in the right dorsolateral prefrontal cortex among the different brain regions of the Brodmann area (p < 0.05). Oxygenated hemoglobin concentrations had consistently negative values for all the treatment combinations, and individual treatment analyses based on single-sample Student’s t-tests showed different degrees of brain activation among channels and Brodmann areas. Meanwhile, a comparison of absolute values indicated that an illuminance level of 500 lx was more comfortable than levels of 300 and 800 lx, and that white color was more comfortable than bulb color and blue color. These results provide a scientific basis for the design of train cars that improve passenger comfort and satisfaction, which is anticipated to enhance the quality of railway services. Full article
(This article belongs to the Topic Indoor Air Quality and Built Environment)
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13 pages, 2469 KiB  
Article
The Effect of Thyroid Lobe Volume on the Common Carotid Artery Blood Flow in Thyroidectomy Position
by Neslihan Hatınoğlu and Basar Erdivanli
J. Clin. Med. 2025, 14(5), 1743; https://doi.org/10.3390/jcm14051743 - 5 Mar 2025
Viewed by 635
Abstract
Background/Objectives: This study investigates the effect of thyroid lobe size on common carotid artery hemodynamics during thyroidectomy. While prior research has reported reduced carotid blood flow during the procedure, the impact of thyroid size remains unclear. We hypothesized that larger thyroid lobes [...] Read more.
Background/Objectives: This study investigates the effect of thyroid lobe size on common carotid artery hemodynamics during thyroidectomy. While prior research has reported reduced carotid blood flow during the procedure, the impact of thyroid size remains unclear. We hypothesized that larger thyroid lobes may influence carotid flow dynamics via external compression. Methods: Adult patients undergoing elective thyroidectomy were prospectively included. Doppler ultrasonography measured carotid artery diameters and flow characteristics at three time points: before anesthesia induction, after induction, and after surgical positioning. Regional cerebral oximetry was recorded. Each carotid artery was analyzed separately. Results: Data from 202 carotid arteries (132 patients) were analyzed. Baseline carotid diameters and flow velocities were similar between patients with normal and large thyroid lobes. Anesthesia induction reduced flow velocities in all patients. After surgical positioning, patients with large thyroid lobes had significantly increased peak systolic velocity, leading to an overestimation of carotid blood flow, when using formula-based calculations. Manually traced Velocity Time Integral confirmed the increase in peak systolic velocity and a shortened systolic/diastolic ratio in these patients. Receiver operating characteristic analysis identified a thyroid lobe volume cutoff of 19.7 mL (AUC: 0.93, Sensitivity: 85%, Specificity: 98%). Regional cerebral oxygen saturation remained unchanged (p > 0.05). Conclusions: Larger thyroid lobes are associated with altered carotid flow dynamics during thyroidectomy, emphasizing diastolic flow. While these findings provide insight into thyroid-related hemodynamic changes, their applicability to patients with pre-existing carotid stenosis or peripheral artery disease remains uncertain, as our study population did not include such cases. Full article
(This article belongs to the Section Anesthesiology)
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