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The cognitive decline associated with chronic metabolic disease diabetes has garnered extensive scrutiny, yet its pathogenesis remains incompletely understood, and the advancement of targeted therapeutics has posed a persistent challenge. Ferroptosis, a novel form of cell death characterized by intracellular lipid peroxidation and iron overload, has recently emerged as a significant factor. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetes-induced cognitive impairment. Numerous contemporary studies have corroborated that ferroptosis within the neurovascular unit is intimately associated with the onset of diabetic cognitive impairment (DCI). This article initially conducts a profound analysis of the mechanism of ferroptosis, followed by a detailed elucidation of the specific manifestations of neurovascular unit ferroptosis in the context of diabetic cognitive function impairment. Furthermore, an exhaustive review of pertinent literature from April 2020 to March 2024 has been undertaken, resulting in the selection of 31 documents of significant reference value. These documents encompass studies on 11 distinct drugs, all of which are centered around investigating methods to inhibit the ferroptosis pathway as a potential treatment for DCI. Simultaneously, we conducted a review of 12 supplementary literary sources that presented 10 pharmacological agents with anti-ferroptosis properties in other neurodegenerative disorders. This article critically examines the potential influence of neurovascular unit ferroptosis on the progression of cognitive impairment in diabetes, from the three aforementioned perspectives, and organizes the existing and potential therapeutic drugs. It is our aspiration that this article will serve as a theoretical foundation for scholars in related disciplines when conceptualizing, investigating, and developing novel clinical drugs for DCI.

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The mechanisms of secondary injury following spinal cord injury are complicated. The role of ferroptosis, which is a newly discovered form of regulated cell death in the neurovascular unit(NVU), is increasingly important. Ferroptosis inhibitors have been shown to improve neurovascular homeostasis and attenuate secondary spinal cord injury(SCI). This review focuses on the mechanisms of ferroptosis in NVU cells and NVU-targeted therapeutic strategies according to the stages of SCI, and analyzes possible future research directions.

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BACKGROUND: The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. METHODS: Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). RESULTS: Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), and junctional adhesion molecule-1 (JAM-1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRß and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. CONCLUSIONS: SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately.

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The retina transforms light into electrical signals, which are sent to the brain via the optic nerve to form our visual perception. This complex signal processing is performed by the retinal neuron and requires a significant amount of energy. Since neurons are unable to store energy, they must obtain glucose and oxygen from the bloodstream to produce energy to match metabolic needs. This process is called neurovascular coupling (NVC), and it is based on a precise mechanism that is not totally understood. The discovery of fine tubular processes termed tunnelling nanotubes (TNTs) set a new type of cell-to-cell communication. TNTs are extensions of the cellular membrane that allow the transfer of material between connected cells. Recently, they have been reported in the brain and retina of living mice, where they connect pericytes, which are vascular mural cells that regulate vessel diameter. Accordingly, these TNTs were termed interpericyte tunnelling nanotubes (IPTNTs), which showed a vital role in blood delivery and NVC. In this chapter, we review the involvement of TNTs in NVC and discuss their implications in retinal neurodegeneration.

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Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

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BACKGROUND: Vestibular paroxysmia is defined by spontaneous, recurrent, short, paroxysmal episodes of vertigo. The authors present a case of vestibular paroxysmia caused by neurovascular compression of the vestibulocochlear nerve due to the subarcuate artery, which was successfully treated with microvascular decompression. OBSERVATIONS: A 46-year-old man first experienced vertigo attacks 5 years earlier. The attacks became more frequent, and left-sided tinnitus developed over the past 4 months, prompting a referral to our hospital. Carbamazepine treatment alleviated symptoms but had to be discontinued due to rash. Brain magnetic resonance imaging and angiography revealed that the left anterior inferior cerebellar artery was pressing on the cisternal segment of the left vestibulocochlear nerve. The authors diagnosed vestibular paroxysmia caused by neurovascular compression and performed microvascular decompression. During the operation, a subarcuate artery was identified as the offending vessel, with a prominent indentation on the vestibulocochlear nerve. The vertigo was completely relieved following surgery. LESSONS: Neurovascular compression of the vestibulocochlear nerve by the subarcuate artery can result in vestibular paroxysmia. https://thejns.org/doi/abs/10.3171/CASE24239.

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An estimated 6.8 million people in the United States have an unruptured intracranial aneurysms, with approximately 30,000 people suffering from intracranial aneurysms rupture each year. Despite the development of population-based scores to evaluate the risk of rupture, retrospective analyses have suggested the limited usage of these scores in guiding clinical decision-making. With recent advancements in imaging technologies, artery wall motion has emerged as a promising biomarker for the general study of neurovascular mechanics and in assessing the risk of intracranial aneurysms. However, measuring arterial wall deformations in vivo itself poses several challenges, including how to image local wall motion and deriving the anisotropic wall strains over the cardiac cycle. To overcome these difficulties, we first developed a novel in vivo MRI-based imaging method to acquire cardiac gated images of the human basilar artery (BA) over the cardiac cycle. Next, complete BA endoluminal surfaces from each frame were segmented, producing high-resolution point clouds of the endoluminal surfaces. From these point clouds we developed a novel B-spline-based surface representation, then exploited the local support nature of B-splines to determine the local endoluminal surface strains. Results indicated distinct regional and temporal variations in BA wall deformation, highlighting the heterogeneous nature BA function. These included large circumferential strains (up to ∼ 20 % ), and small longitudinal strains, which were often contractile and out of phase with the circumferential strains patterns. Of particular interest was the temporal phase lag in the maximum circumferential perimeter length, which indicated that the BA deforms asynchronously over the cardiac cycle. In summary, the proposed method enabled local deformation analysis, allowing for the successful reproduction of local features of the BA, such as regional principal stretches, areal changes, and pulsatile motion. Integrating the proposed method into existing population-based scores has the potential to improve our understanding of mechanical properties of human BA and enhance clinical decision-making.

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INTRODUCTION: Lisfranc injuries are uncommon but frequently misdiagnosed and carry a high rate of morbidity. OBJECTIVE: This review highlights the pearls and pitfalls of Lisfranc injuries, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Lisfranc injuries are caused by high- or low-energy trauma to the tarsometatarsal (TMT) joint complex. The severity of injury exists on a spectrum, ranging from minor subluxations to fractures and dislocations involving the TMT joint complex. They can be complicated by compartment syndrome, neurovascular compromise, and open fractures. Prompt diagnosis is critical in preventing chronic pain and mobility challenges, as even small subluxations can result in significant morbidity. Lisfranc injuries should be considered in all patients with a foot injury. Patients with Lisfranc injuries most commonly present with midfoot pain, swelling, or ecchymosis. Despite the importance of a timely diagnosis, Lisfranc injuries are commonly missed on plain radiographs due to their often subtle findings. When x-rays are negative but there is significant clinical suspicion, emergency clinicians should obtain advanced imaging such as computed tomography to aid in diagnosis. All Lisfranc injuries should be discussed with orthopedic surgery to determine definitive management. Patients who can be discharged should be made non-weightbearing and placed in a short-leg splint. CONCLUSION: The consideration of Lisfranc injuries can help emergency clinicians make a timely diagnosis to prevent future complications.

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Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.g., resting-state functional connectivity [RSFC]) because it is unclear whether changes in NMC/NVC affect RSFC measures. We leverage wide-field optical imaging in Thy1-jRGECO1a mice to map cortical calcium activity in pyramidal neurons, flavoprotein autofluorescence (representing oxidative metabolism), and hemodynamic activity during wake and ketamine/xylazine anesthesia. Spontaneous dynamics of all contrasts exhibit patterns consistent with RSFC. NMC/NVC relative to excitatory activity varies over the cortex. Ketamine/xylazine profoundly alters NVC but not NMC. Compared to awake RSFC, ketamine/xylazine affects metabolic-based connectomes moreso than hemodynamic-based measures of RSFC. Anesthesia-related differences in NMC/NVC timing do not appreciably alter RSFC structure.

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BACKGROUND: The cranial nerve (CN) V and adjacent neurovascular structures are crucial landmarks in microvascular decompression (MVD). MVD of CN V is the most effective treatment for patients with drug-resistant trigeminal neuralgia (TN) diagnosis. The endoscope-assisted retrosigmoid approach (RSA) provides better exposure and less cerebellar retraction in the corridor towards the cerebellopontine angle (CPA). METHODS: Five adult cadaver heads (10 sides) underwent dissection of the MVD in park bench position. MVD was simulated using microsurgical RSA, and the anatomical landmarks were defined. Microsurgical dissections were additionally performed along the endoscopic surgical path. Additionally, we present an illustrative case with TN caused by anterior inferior cerebellar artery (AICA) compression. The CN V and its close relationships were demonstrated. Endoscopic and microscopic three-dimensional pictures were obtained. RESULTS: This study increases the anatomical and surgical orientation for CN V and surrounding structures. The CN V arises from the lateral part of the pons and runs obliquely upward toward the petrous apex. It has motor roots that leave from pons antero-supero-medial direction to the sensory root. The endoscopic instruments provide perfect visualization with minimal cerebellar retraction during MVD. CONCLUSION: MVD surgically targets the offending vessel(s) leading to TN and aims to create a disconnected area. The combination of preoperative radiographic assessment with and anatomical correlation provides safe and effective application while facilitating selection of the most appropriate approach. The RSA allows satisfactory visualization for CN V. Endoscope-assisted microsurgery through the CPA is a challenge, it should be performed with advanced anatomical knowledge.

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Ischemic stroke has garnered global medical attention as one of the most serious cerebrovascular diseases. The mechanisms involved in both the development and recovery phases of ischemic stroke are complex, involving intricate interactions among different types of cells, each with its own unique functions. To better understand the possible pathogenesis, neurovascular unit (NVU), a concept comprising neurons, endothelial cells, mural cells, glial cells, and extracellular matrix components, has been used in analysing various brain diseases, particularly in ischemic stroke, aiming to depict the interactions between cerebral vasculature and neural cells. While in vivo models often face limitations in terms of reproducibility and the ability to precisely mimic human pathophysiology, it is now important to establish in vitro NVU models for ischemic stroke research. In order to accurately portray the pathological processes occurring within the brain, a diverse array of NVU 2D and 3D in vitro models, each possessing unique characteristics and advantages, have been meticulously developed. This review presents a comprehensive overview of recent advancements in in vitro models specifically tailored for investigating ischemic stroke. Through a systematic categorization of these developments, we elucidate the intricate links between NVU components and the pathogenesis of ischemic stroke. Furthermore, we explore the distinct advantages offered by innovative NVU models, notably 3D models, which closely emulate in vivo conditions. Additionally, an examination of current therapeutic modalities for ischemic stroke developed utilizing in vitro NVU models is provided. Serving as a valuable reference, this review aids in the design and implementation of effective in vitro models for ischemic stroke research.

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Through numerical modeling, it has been determined that near infrared spectroscopy with a frequency domain approach can detect neurovascular structures with diameters from 0.5 mm at source-detector distances of 5-8 mm, depending on optical parameters and technical implementation of the method. Among the five classical machine learning methods considered, quadratic discriminant analysis is the most effective for detection. Furthermore, it has been demonstrated that the use of a photomultiplier tube and the registration of both amplitude and phase signal components exhibit the highest sensitivity. Spectroscopy can rival modern ultrasound for detecting arterial vessels. A cross-shaped probe configuration improves sensitivity, and the ratio of reduced scattering coefficient values at different wavelengths is informative for blood-filled vessel detection. These findings are consistent with and significantly extend previous experimental in vivo and in situ studies and could be valuable for intraoperative diagnostic tasks, particularly in neurosurgery.

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The Blood Oxygenation Level-Dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFP) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ~10%. Such experiments have not been performed in humans. As an approximation, we recorded (in the same subject, N = 57 healthy participants) at a task-free, resting state the BOLD signal and, in a different session, the magnetoencephalographic (MEG) signal, which reflects purely neural (synaptic) events. We then calculated the turnover of these signals by computing the successive moment-to-moment difference in the BOLD and MEG time series and retaining the median of the absolute value of the differenced series (TBOLD and TMEG, respectively). A linear regression of normalized TBOLD vs. TMEG revealed that ~30% of TMEG contributes to TBOLD, accounting for 11.3% of the latter's variance. This percentage estimate is close to the ~10% estimate above obtained by direct recordings in animal experiments.

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Neurovascular compression syndrome (NVCS), characterized by cranial nerve compression due to adjacent blood vessels at the root entry zone, frequently presents as trigeminal neuralgia (TN), hemifacial spasm (HFS), or glossopharyngeal neuralgia (GN). Despite its prevalence in NVCS assessment, Magnetic Resonance Tomographic Angiography (MRTA)'s limited sensitivity to small vessels and veins poses challenges. This study aims to refine vessel localization and surgical planning for NVCS patients using a novel 3D multimodal fusion imaging (MFI) technique incorporating computed tomography angiography and venography (CTA/CTV). A retrospective analysis was conducted on 76 patients who underwent MVD surgery and were diagnosed with single-site primary TN, HFS, or GN. Imaging was obtained from MRTA and CTA/CTV sequences, followed by image processing and 3D-MFI using FastSurfer and 3DSlicer. The CTA/CTV-3D-MFI showed higher sensitivity than MRTA-3D-MFI in predicting responsible vessels (98.6% vs. 94.6%) and NVC severity (98.6% vs. 90.8%). Kappa coefficients revealed strong agreement with MRTA-3D-MFI (0.855 for vessels, 0.835 for NVC severity) and excellent agreement with CTA/CTV-3D-MFI (0.951 for vessels, 0.952 for NVC). Resident neurosurgeons significantly preferred CTA/CTV-3D-MFI due to its better correlation with surgical reality, clearer depiction of surgical anatomy, and optimized visualization of approaches (p < 0.001). Implementing CTA/CTV-3D-MFI significantly enhanced diagnostic accuracy and surgical planning for NVCS, outperforming MRTA-3D-MFI in identifying responsible vessels and assessing NVC severity. This innovative imaging modality can potentially improve outcomes by guiding safer and more targeted surgeries, particularly in cases where MRTA may not adequately visualize crucial neurovascular structures.

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Entrapment neuropathy of the median nerve is typically caused by compression at specific anatomical points. However, idiopathic cases, where the standard anatomical compression points are normal, pose diagnostic challenges. This report highlights a unique case discovered during an anatomical dissection of the right upper limb in a 62-year-old male cadaver, where the median nerve was compressed by an unusual branch of the brachial artery, termed the superficial brachioulnar artery (SBUA). The median nerve formed at the distal half of the arm, receiving additional components from the lateral cord, with a noted communication with the musculocutaneous nerve. The SBUA, originating from the brachial artery, passed between the roots of the median nerve and continued superficially, forming the superficial palmar arch. The coexistence of neurovascular variations is clinically significant as it may lead to nerve compression and subsequent symptoms. This case is the first documented instance of median nerve compression by an SBUA. Such variations are crucial for surgical and diagnostic procedures, as abnormal vascular structures can be mistaken for veins, leading to iatrogenic injuries. In addition, understanding these variations helps explain idiopathic median nerve neuropathies and highlights the need for thorough anatomical knowledge to prevent complications during surgical interventions.

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An 89-year-old Caucasian male cadaver with prostate cancer demonstrated bilateral persistence of the median artery and bifid median nerve (BMN) during upper limb dissection. The persistent median artery (PMA) originated from the common interosseous artery and coursed alongside the median nerve. Proximal to the carpal tunnel, the median nerve bifurcated into medial and lateral branches. To our knowledge, this is the first documented case of a bilateral PMA and BMN. While the majority of existing literature focuses on a unilateral PMA or unilateral BMN, bilateral occurrences of either variation are rare. This report presents a novel finding by documenting the simultaneous presence of a bilateral PMA and BMN.

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CNS diseases associated with compromised blood supply and/or vascular integrity are one of the leading causes of mortality and disability in adults worldwide and are also among 10 most common causes of death in children. Angiogenesis is an essential element of regeneration processes upon nervous tissue damage and can play a crucial role in neuroprotection. Here we review the features of cerebral vascular regeneration after ischemic stroke, including the complex interactions between endothelial cells and other brain cell types (neural stem cells, astrocytes, microglia, and oligodendrocytes). The mechanisms of reciprocal influence of angiogenesis and neurogenesis, the role of astrocytes in the formation of the blood-brain barrier, and roles of microglia and oligodendrocytes in vascular regeneration are discussed. Understanding the mechanisms of angiogenesis regulation in CNS is of critical importance for the development of new treatments of neurovascular pathologies.

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Familial dysautonomia (FD) is a rare genetic neurodevelopmental and neurodegenerative disorder. In addition to the autonomic and peripheral sensory neuropathies that challenge patient survival, one of the most debilitating symptoms affecting patients' quality of life is progressive blindness resulting from the steady loss of retinal ganglion cells (RGCs). Within the FD community, there is a concerted effort to develop treatments to prevent the loss of RGCs. However, the mechanisms underlying the death of RGCs are not well understood. To study the mechanisms underlying RGC death, Pax6-cre;Elp1loxp/loxp male and female mice and postmortem retinal tissue from an FD patient were used to explore the neuronal and non-neuronal cellular pathology associated with the FD optic neuropathy. Neurons, astrocytes, microglia, Müller glia, and endothelial cells were investigated using a combination of histological analyses. We identified a novel disruption of cellular homeostasis and gliosis in the FD retina. Beginning shortly after birth and progressing with age, the FD retina is marked by astrogliosis and perturbations in microglia, which coincide with vascular remodeling. These changes begin before the onset of RGC death, suggesting alterations in the retinal neurovascular unit may contribute to and exacerbate RGC death. We reveal for the first time that the FD retina pathology includes reactive gliosis, increased microglial recruitment to the ganglion cell layer (GCL), disruptions in the deep and superficial vascular plexuses, and alterations in signaling pathways. These studies implicate the neurovascular unit as a disease-modifying target for therapeutic interventions in FD.

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BACKGROUND: Pathophysiological mechanisms underlying cognitive impairment in end-stage renal disease (ESRD) remain unclear, with limited studies on the temporal variability of neural activity and its coupling with regional perfusion. PURPOSE: To assess neural activity and neurovascular coupling (NVC) in ESRD patients, evaluate the classification performance of these abnormalities, and explore their relationships with cognitive function. STUDY TYPE: Prospective. POPULATION: Exactly 33 ESRD patients and 35 age, sex, and education matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: The 3.0T/3D pseudo-continuous arterial spin labeling, resting-state functional MRI, and 3D-T1 weighted structural imaging. ASSESSMENT: Dynamic (dfALFF) and static (sfALFF) fractional amplitude of low-frequency fluctuations and cerebral blood flow (CBF) were assessed. CBF-fALFF correlation coefficients and CBF/fALFF ratio were determined for ESRD patients and HCs. Their ability to distinguish ESRD patients from HCs was evaluated, alongside assessment of cerebral small vessel disease (CSVD) MRI features. All participants underwent blood biochemical and neuropsychological tests to evaluate cognitive decline. STATISTICAL TESTS: Chi-squared test, two-sample t-test, Mann-Whitney U tests, covariance analysis, partial correlation analysis, family-wise error, false discovery rate, Bonferroni correction, area under the receiver operating characteristic curve (AUC) and multivariate pattern analysis. P < 0.05 denoted statistical significance. RESULTS: ESRD patients exhibited higher dfALFF in triangular part of left inferior frontal gyrus (IFGtriang) and left middle temporal gyrus, lower CBF/dfALFF ratio in multiple brain regions, and decreased CBF/sfALFF ratio in bilateral superior temporal gyrus (STG). Compared with CBF/sfALFF ratio, dfALFF, and sfALFF, CBF/dfALFF ratio (AUC = 0.916) achieved the most powerful classification performance in distinguishing ESRD patients from HCs. In ESRD patients, decreased CBF/fALFF ratio correlated with more severe renal impairment, increased CSVD burden, and cognitive decline (0.4 < |r| < 0.6). DATA CONCLUSION: ESRD patients exhibited abnormal dynamic brain activity and impaired NVC, with dynamic features demonstrating superior discriminative capacity and CBF/dfALFF ratio showing powerful classification performance. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.