Pathological changes in neurovascular units: Lessons from cases of vascular dementia

Li, Chao; Wang, Yan; Yan, Xiaofeng; Guo, Zhen‐Ni; Yang, Yi

doi:10.1111/cns.13572

Cited by 32 publications

(19 citation statements)

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“…Neural cells have high metabolic demands and the brain microvascular system has essential roles to play in their nutrition, in what has been termed the neurovascular unit [ 60 , 62 ]. The essential roles of the coupled neurovascular system in neural health become apparent in neurodegenerative disorders and in ischaemic stroke when this system is disrupted [ 63 , 64 , 65 , 66 , 67 , 68 ]. Glypican-3 also has important roles in neural network development, controlling netrin-mediated axonal guidance [ 63 ]; the syndecans also act as cell surface receptors interacting with Slit-roundabout neural guidance proteins during neural network formation [ 53 , 54 , 69 , 70 , 71 ].…”

Section: Introductionmentioning

confidence: 99%

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

Melrose

Hayes

Bix

2021

IJMS

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Background. The extracellular matrix of the PNS/CNS is unusual in that it is dominated by glycosaminoglycans, especially hyaluronan, whose space filling and hydrating properties make essential contributions to the functional properties of this tissue. Hyaluronan has a relatively simple structure but its space-filling properties ensure micro-compartments are maintained in the brain ultrastructure, ensuring ionic niches and gradients are maintained for optimal cellular function. Hyaluronan has cell-instructive, anti-inflammatory properties and forms macro-molecular aggregates with the lectican CS-proteoglycans, forming dense protective perineuronal net structures that provide neural and synaptic plasticity and support cognitive learning. Aims. To highlight the central nervous system/peripheral nervous system (CNS/PNS) and its diverse extracellular and cell-associated proteoglycans that have cell-instructive properties regulating neural repair processes and functional recovery through interactions with cell adhesive molecules, receptors and neuroregulatory proteins. Despite a general lack of stabilising fibrillar collagenous and elastic structures in the CNS/PNS, a sophisticated dynamic extracellular matrix is nevertheless important in tissue form and function. Conclusions. This review provides examples of the sophistication of the CNS/PNS extracellular matrix, showing how it maintains homeostasis and regulates neural repair and regeneration.

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Section: Introductionmentioning

confidence: 99%

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

Melrose

Hayes

Bix

2021

IJMS

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“…VaD reaches its peak in ischemic brain injury (5). In addition to vascular problems, risk factors such as diabetes, age, smoking, and alcohol cannot be ignored (6). Improving vascular endothelial dysfunction and restoring the increase in oxidative stress and neuroinflammation caused by hypoperfusion may provide a potential treatment strategy for preventing the cognitive dysfunction of VaD.…”

Section: Introductionmentioning

confidence: 99%

Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted gene coexpression network analysis

et al. 2021

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Background: To date, vascular dementia (VaD) lacks effective treatment in clinical practice. There is also growing evidence that VaD may be closely related to the immune response. The development of highthroughput technology, and the recently discovered group of new mediators called competitive endogenous RNAs (ceRNA), provides a unique opportunity to study the immunomodulation of VaD.Methods: In this study, we used gene expression profiles in the Gene Expression Omnibus (GEO) database to obtain immune-related gene coexpression modules through a weighted gene coexpression network analysis (WGCNA) and gene enrichment analysis. We extracted and merged long non-coding RNA (lncRNA) and microRNA (miRNA) expressions from the GEO database and mapped them with related databases.Subsequently, we used Cytoscape to construct a lncRNA-miRNA-mRNA network, and then we performed an enrichment analysis on the mRNAs in the network to determine their regulatory function. Subsequently, we used an ImmuCellAI immune infiltration analysis and constructed a ceRNA sub-network of related immune cells. Finally, we conducted a gene set enrichment analysis (GSEA) to determine the potential regulatory pathways of the key factors.Results: As a result, we identified the blue module as the key module of immunity and constructed the related CeRNA network. Immune infiltration analysis showed that natural killer T (NKT) cells may be the key immune cells of VaD. Using a Pearson correlation analysis, we identified that B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1 may be the key factors of VaD. Our subsequent GSEA analysis showed that lncRNA NEAT1 may be regulated by NK cells and toll-like receptors.Conclusions: Our research provides new therapeutic targets for vascular dementia from the immunological perspective for the first time, including B4GALT1, PPP1R3B, MICB, HHAT, DSC2, DNA2, SCARA3, and lncRNA NEAT1, and our research hopes to provide new treatment options for VaD.

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“…There is some evidence that a decrease of cerebral blood flow (CBF) causes a series of changes in the neurovascular unit (NVU), such as impaired neuronal function, abnormal activation of glial cells, and changes in vascular permeability, all of which collectively play a role in the pathogenesis of VD [ 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

Risk factors for cognitive decline in type 2 diabetes mellitus patients in Brazil: a prospective observational study

Faria

Dall’Agnol

Gouveia

et al. 2022

Diabetol Metab Syndr

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Background Type 2 Diabetes Mellitus (T2DM) patients are twice as likely to develop dementia. The study’s goal was to evaluate cognitive performance and risk factors for cognitive decline in this population. Methods Prospective observational study was conducted with 400 T2DM adults, of whom, during routine baseline and follow-up appointments, had socio-demographic, clinical, and laboratory data collected, and underwent physical examination, screening for depression symptoms (Patient Health Questionaire-9-PHQ-9), and cognitive tests: Mini-Mental State Examination (MMSE), Semantic Verbal Fluency Test, Trail Making Test A/B, and Word Memory Tests. Each cognitive test score was converted to a z-score and its average resulted in a new variable called Global Cognitive z-Score [GCS(z)]. Averages of the cognitive test scores and GCS(z) at both moments were compared by the Student’s T-Test for paired samples. Multivariate binary logistic regression models were built to assess the association of GCS(z) < zero with risk factors for cognitive decline at the baseline and follow-up. Results After exclusions, 251 patients were eligible, being 56.6% female, mean age of 61.1 (± 9.8) years, 12.6 (± 8.9) years of DM duration, and 7.6 (± 4.2) years of school education. Follow-up had 134 patients reevaluated and took place after a mean of 18.4(± 5.0) months. Eleven (14%) patients with a GCS(z) ≥ 0 at baseline turned into a GCS(z) < 0 at follow-up. There were no significant differences between the means of cognitive test scores and GCS(z) at the two evaluation moments. At the baseline, the multivariate logistic regression model identified five risk factors associated with GCS(z) < zero: age ≥ 65 years, schooling ≤ 6 years, arterial hypertension, depression symptoms, and diabetic retinopathy (DR), with odds ratio (OR) and 95% confidence interval (CI95%) respectively: 5.46 (2.42–12.34); 12.19 (5.62–26.46); 2.55 (0.88–7.39); 3.53 (1.55–8.07) e 2.50 (1.18–5.34). At follow-up, the risk factors for GCS(z) < zero were: schooling ≤ 6 years, DM duration ≥ 10 years, depression symptoms, arterial hypertension, and cardiovascular disease (CVD), OR and CI95% respectively: 10.15 (3.68–28.01); 2.68 (0.96–7.48); 4.92 (1.77–13.70); 7.21 (1.38–35.71) e 5.76 (1.93–17.18). Conclusions Based on our results, cognitive evaluation and follow-up should be incorporated on the routine of T2DM patients, especially for those with advanced age, low education level, prolonged DM duration, arterial hypertension, depression symptoms, CVD, and DR.

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Pathological changes in neurovascular units: Lessons from cases of vascular dementia

Cited by 32 publications

References 135 publications

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

Construction of a ceRNA immunoregulatory network related to the development of vascular dementia through a weighted gene coexpression network analysis

Risk factors for cognitive decline in type 2 diabetes mellitus patients in Brazil: a prospective observational study

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