Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves

Cardiovascular Diabetology, Год журнала: 2023, Номер 22(1)

Опубликована: Ноя. 15, 2023

Abstract Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network microvessels beyond well-known documented target organs, i.e., retina, kidney, peripheral nerves. Indeed, an intact microvascular bed crucial for preserving each organ’s specific functions achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related dysfunction leads widespread multiorgan consequences in still-overlooked non-traditional organs such as brain, lung, bone tissue, skin, arterial wall, heart, or musculoskeletal system. All these are vulnerable physiopathological mechanisms that cause damage diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, endothelial dysfunction) collectively contribute microvessels’ structure function, compromising blood flow tissue perfusion. However, microcirculatory networks differ between due variations haemodynamic, vascular architecture, affected cells, resulting spectrum clinical presentations. The aim this review focus on multifaceted nature impairment through available evidence often overlooked organs. A better understanding microangiopathy non-target provides broader perspective systemic disease, underscoring importance recognising comprehensive range complications classic sites.

Язык: Английский

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Research Progress in the Pathogenesis of Cognitive Dysfunction in White Matter Hyperintensities: A Narrative Review

Journal of Integrative Neuroscience, Год журнала: 2025, Номер 24(2)

Опубликована: Фев. 19, 2025

Cerebral small vessel disease is a common endangering human health due to its insidious and repeated onset progressive aggravation. White matter hyperintensities (WMHs) are one of the classic imaging markers cerebral disease. The term 'WMHs' was first proposed by Hachinski in 1987. WMHs our study mainly refer white damage caused various vascular factors, known as vascularized hyperintensity. significantly correlated with stroke, cognitive dysfunction, emotional disturbance, gait abnormality, have drawn widespread attention. This article reviews research progress on pathogenesis dysfunction associated provides theoretical reference for understanding early assessment dysfunction.

Язык: Английский

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Ceramide in cerebrovascular diseases

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 2, 2023

Ceramide, a bioactive sphingolipid, serves as an important second messenger in cell signal transduction. Under stressful conditions, it can be generated from de novo synthesis, sphingomyelin hydrolysis, and/or the salvage pathway. The brain is rich lipids, and abnormal lipid levels are associated with variety of disorders. Cerebrovascular diseases, which mainly caused by cerebral blood flow secondary neurological injury, leading causes death disability worldwide. There growing body evidence for close connection between elevated ceramide cerebrovascular especially stroke small vessel disease (CSVD). increased has broad effects on different types cells, including endothelial microglia, neurons. Therefore, strategies that reduce such modifying sphingomyelinase activity or rate-limiting enzyme synthesis pathway, serine palmitoyltransferase, may represent novel promising therapeutic approaches to prevent treat injury-related diseases.

Язык: Английский

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Edaravone dexborneol ameliorates cognitive impairment by regulating the NF-κB pathway through AHR and promoting microglial polarization towards the M2 phenotype in mice with bilateral carotid artery stenosis (BCAS)

European Journal of Pharmacology, Год журнала: 2023, Номер 957, С. 176036 - 176036

Опубликована: Сен. 4, 2023

Язык: Английский

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Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke

Journal of Inflammation Research, Год журнала: 2023, Номер Volume 16, С. 311 - 319

Опубликована: Янв. 1, 2023

Background: White matter hyperintensity (WMH) is associated with risk of acute ischemic stroke (AIS) and poor outcomes after AIS. The purpose this prospective study was to evaluate the association between serum YKL-40 levels WMH burden in patients Methods: From February 2020 March 2021, a total 672 consecutive AIS magnetic resonance imaging data were prospectively recruited form two centers. Serum quantified using enzyme-linked immunosorbent assay. semiquantitatively measured by Fazekas visual grading scale. According severity overall WMH, dichotomized into none–mild group (Fazekas score 0– 2) or moderate–severe 3– 6). Besides, based on periventricular (PV-WMH) deep (D-WMH), categorized as 1) 2– 3). Results: Among patients, 335 (49.9%) participants identified 326 (48.5%) PV-WMH 262 (39.0%) D-WMH. Compared first quartile YKL-40, adjusted odds ratio (OR) fourth for 2.473 (95% confidence interval [CI] 1.316– 4.646; P =0.005). No significant observed (OR 0.762; 95% CI 0.434– 1.336; =0.343) D-WMH 0.695; 0.413– 1.171; =0.172). Conclusion: Our results suggested that higher appeared be PV-WMH, but not Keywords: stroke, white hyperintensities, biomarkers

Язык: Английский

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Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood–Brain Barrier Dysfunction/Disruption with Increased Risk of Hemorrhagic and Ischemic Stroke

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1463 - 1463

Опубликована: Июль 1, 2024

Globally, cerebral microbleeds (CMBs) are increasingly being viewed not only as a marker for small vessel disease (SVD) but also having an increased risk the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation dysfunction blood–brain barrier and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, evolution CMBs. CMBs known disorder microvessels that visualized 3–5 mm, smooth, round, or oval, hypointense (black) lesions seen on T2*-weighted gradient recall echo susceptibility-weighted sequences MRI images. occur high prevalence in community-dwelling older individuals. Since our current global population is oldest recorded history expected continue grow, we can expect healthcare burdens grow. Increased numbers (≥10) should raise red flag regarding large symptomatic neurologic intracerebral hemorrhages. Importantly, currently regarded markers diffuse vascular neurodegenerative damage. Herein author highlights it essential learn much about CMB development, evolution, their relation impaired cognition, dementia, exacerbation neurodegeneration.

Язык: Английский

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Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease

Stroke, Год журнала: 2023, Номер 54(5), С. 1367 - 1376

Опубликована: Апрель 24, 2023

Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As central hub of the structural network, role thalamus in SVD-related impairments remains unclear. We aimed to determine associations between alterations thalamic subregions and SVD.In this cross-sectional study, 205 SVD participants without lacunes from third follow-up (2020) prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor Magnetic Resonance Cohort), was initiated 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, memory. Probabilistic tractography performed 6 cortical regions, followed connectivity-based segmentation assess each subregion volume connectivity (measured mean diffusivity [MD] connecting white matter tracts) with cortex. Least absolute shrinkage selection operator regression analysis conducted identify volumes or total that have strongest association performance. Linear mediation analyses test least operator-selected MD performance, while adjusting for age education.We found higher thalamic-motor tract associated worse speed (β=-0.27; P<0.001), thalamic-frontal function (β=-0.24; P=0.001), memory (β=-0.28; respectively. The showed thalamocortical tracts mediated corresponding performances 3 domains.Our results suggest are linked impairment SVD, largely depending on pattern specific regions.

Язык: Английский

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Therapeutic potential of mesenchymal stem cells for cerebral small vessel disease

Regenerative Therapy, Год журнала: 2024, Номер 25, С. 377 - 386

Опубликована: Фев. 22, 2024

Cerebral small vessel disease (CSVD), as the most common, chronic and progressive vascular on brain, is a serious neurological disease, whose pathogenesis remains unclear. The leading cause of stroke cognitive impairment dementia, contributes to about 20% strokes, including 25% ischemic strokes 45% dementias. Undoubtedly, high incidence poor prognosis CSVD have brought heavy economic medical burden society. present treatment focuses management risk factors. Although factors may be important causes or accelerators should always treated in accordance with best clinical practice, controlling alone could not curb progression brain injury. Therefore, developing safer more effective strategies for urgently needed. Recently, mesenchymal stem cells (MSCs) therapy has become an emerging therapeutic modality central nervous system given their paracrine properties immunoregulatory. Herein, we discussed potential MSCs CSVD, aiming enable clinicians researchers understand recent progress future directions field.

Язык: Английский

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Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction-Disruption with an Increased Risk of Hemorrhagic and Ischemic Stroke That Is Capable of Exacerbating Neurodegeneration

Опубликована: Май 8, 2024

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also having an increased risk the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation dysfunction blood-brain barrier and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, evolution CMBs. CMBs known disorder microvessels that visualized 3-5mm, smooth, round or oval, hypointense (black) lesions seen on T2*-weighted gradient recall echo susceptibility-weighted sequences MRI images. (a global problem) occur high prevalence in community-dwelling older individuals. Since our current population is oldest recorded history expected continue grow, we can expect health care burdens grow. should raise red flag regarding large symptomatic neurologic intracerebral hemorrhages. Importantly, currently regarded markers diffuse vascular neurodegenerative damage. Thus, it essential try learn much about their development, evolution, relation impaired cognition, dementia, neurodegeneration.

Язык: Английский

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SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(3)

Опубликована: Сен. 18, 2023

Abstract Background and Objective Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase‐9 (MMP‐9), Tissue metalloproteinase‐1 (TIMP‐1), Monocyte Chemoattractant Protein‐1 (MCP‐1) are several that potentially involved in CSVD. In this present study, we aimed to investigate relationship candidate molecules features. Method The concentration each biomarker was measured 79 acute ischemic stroke patients admitted within 72 h after symptom onset. associations blood levels markers score were investigated, well feature, including white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces (EPVS). Results mean age 69.0 ± 11.8 years, 65.8% participants male. Higher SERPINA3 level (>78.90 ng/mL) significantly associated with larger WMH volume higher scores on Fazekas's scale all three models. Multiple regression analyses revealed linear absolute burden level, especially model 3 ( β = 0.14; 95% confidence interval [CI], 0.04–0.24 p ). Restricted cubic spline demonstrated dose–response nonlineariy 0.0366 0.0378 2 mode 3, respectively). Using receiving operating characteristic (ROC) curve, plasma 64.15 ng/mL distinguished >7.8 mL highest sensitivity specificity (75.92% 60%, respectively, area under curve [AUC] 0.668, 0.0102). No statistically significant been found other Conclusion summary, among four at baseline severity, which novel validated its inflammation endothelial dysfunction.

Язык: Английский

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