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Axonal degeneration and retinal neurovascular dysfunction in the TgF344-AD rat model of Alzheimer's disease.

BackgroundRecent research suggests that retinal changes occur at early stages of Alzheimer's disease (AD). However, gaps remain in understanding the detailed pathophysiological processes and their molecular underpinnings.ObjectiveThis study investigates alterations in the retinal neurovascular unit (NVU) and associated proteomic changes in the TgF344-AD rat model to determine how these changes relate to brain and known AD pathology.MethodsTransgenic rats and age-matched wild-type rats were studied. Proteomic analysis was conducted to identify changes in critical signaling pathways across the r

Понимание барьера мозга в крови: от физиологии к патологии.

Барьер мозга крови (BBB) представляет собой высокоспециализированную структуру, которая отделяет циркуляцию крови от мозга, обеспечивая защиту, гомеостаз и оптимальное функционирование центральной нервной системы (CNS). Церебральные эндотелиальные клетки, перициты, астроциты и подземная мембрана образуют BBB. Взаимодействие этих элементов с нейронами и микроглией называется нейроваскулярной единицей (NVU). Каждый компонент играет основополагающую роль в поддержании целостности и функционирования ББД. Такая избирательная проницаемость имеет решающее значение для поддержания оптимальной среды дл

Совпадение в аннотации оригинала
The blood-brain barrier (BBB) is a highly specialized structure that separates the circulating blood from the brain, ensuring protection, homeostasis, and optimal functioning of the central nervous system (CNS). Cerebral endothelial cells, pericytes, astrocytes, and basement membrane form the BBB. The interaction of these elements with neurons and microglia …

Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We co

Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery an

Substance P - a regulatory peptide with defense and repair functions. Results and perspectives for the fight against COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early 2020. SARS CoV-2 causes endothelial cell destruction and swelling, microthrombosis, constriction of capillaries, and malfunction of pericytes, all of which are detrimental to capillary integrity, angiogenesis, and healing processes. Cytokine storming has been connected to COVID-19 disease. Hypoxemia and tissue hypoxia may arise from impaired oxygen diffusion exchange in the lungs due to capillary damage and congestion. This pers…

Contrast-Enhanced Ultrasound Imaging Detects Anatomical and Functional Changes in Rat Cervical Spine Microvasculature With Normal Aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. Although these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 months, N = 6) exhibited significant tortuosity in the anterior spinal a

Regulation of the blood-brain barrier function by peripheral cues in health and disease.

The blood-brain barrier (BBB) is formed by microvascular endothelial cells which are ensembled with pericytes, astrocytes, microglia and neurons in the neurovascular unit (NVU) that is crucial for neuronal function. Given that the NVU and the BBB are highly dynamic and regulated structures, their integrity is continuously challenged by intrinsic and extrinsic factors. Herein, factors from peripheral organs such as gonadal and adrenal hormones may influence vascular function also in CNS endothelial cells in a sex- and age-dependent manner. The communication between the periphery and the CNS lik…

High salt diet exacerbates cognitive deficits and neurovascular abnormalities in APP/PS1 mice and induces AD-like changes in wild-type mice.

High salt diet (HSD) is a risk factor of hypertension and cardiovascular disease. Although clinical data do not clearly indicate the relatio … f Aqp-4, and high expression of CD31 in the wild-type mice, which were accompanied with the loss of pericytes (PCs) and increase in blood brain barrier (BBB) permeability. As a result, wild-type mice fed with HSD performed poorly in Morris Water Maze and object recognition test. In the APP/PS1 mice, HSD feeding for 8 months worsen the cognition and accompan …

Endothelial c-Src Mediates Neovascular Tuft Formation in Oxygen-Induced Retinopathy.

Vascular retinopathy, characterized by abnormal blood vessel growth in the retina, frequently results in vision impairment or loss. Neovascular tufts, a distinctive pathologic feature of this condition, are highly leaky blood vessel structures, exacerbating secondary complications. Despite their clinical significance, the mechanisms underlying tuft development are not fully elucidated, posing challenges for effective management and treatment of vascular retinopathy. This study investigates the role of cellular (c)-Src in neovascular tuft formation. Although c-Src is a pivotal regulator in deve

A synergistic approach for modulating the tumor microenvironment to enhance nano-immunotherapy in sarcomas.

The lack of properly perfused blood vessels within tumors can significantly hinder the distribution of drugs, leading to reduced treatment e … ment. Furthermore, the combined therapy normalizes the tumor vasculature by increasing two-fold the pericytes coverage. This combination not only improves six times tumor perfusion but also enhances drug delivery. As a result, blood vessel functionality is enhanced, leading to increased infiltration by 40 % of immune cells (CD4+ and CD8+ T-cells) and improv …

Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.

Acute kidney injury (AKI) is one of the main conditions responsible for chronic kidney disease (CKD), including end-stage renal disease (ESRD) as a long-term complication. Besides short-term complications, such as electrolyte and acid-base disorders, fluid overload, bleeding complications or immune dysfunctions, AKI can develop chronic injuries and subsequent CKD through renal fibrosis pathways. Kidney fibrosis is a pathological process defined by excessive extracellular matrix (ECM) deposition, evidenced in chronic kidney injuries with maladaptive architecture restoration. So far, cited malad

Medullary stromal cells synergize their production and capture of CCL21 for T-cell emigration from neonatal mouse thymus.

The release of newly selected αβT cells from the thymus is key in establishing a functional adaptive immune system. Emigration of the first … f medullary epithelium, CCL21 protein was captured by mesenchymal stroma consisting of integrin α7+ pericytes and CD34+ adventitial cells at sites of thymic exit. This chemokine compartmentalization involved the heparan sulfate-dependent presentation of CCL21 via its C-terminal extension, explaining the absence of a requirement for CCL19, which lacks this d …

Acquired Elastotic Hemangioma-like Change of the Vulva Associated With Lichen Sclerosus.

Acquired elastotic hemangioma (AEH) is a rare variant of hemangioma that usually presents as an asymptomatic, solitary, slow-growing red pla … ed and intertwined by intense elastosis in the reticular dermis. Alpha-smooth muscle actin positive pericytes encircled the vascular channels. The lesion can be understood as a reparative process within an LS with the appearance of epidermal hyperplasia, proliferation of small vascular channels, and hyperplastic elastosis. There is a close link between epid …

Systemic cell therapy for muscular dystrophies : The ultimate transplantable muscle progenitor cell and current challenges for clinical efficacy.

The intrinsic regenerative capacity of skeletal muscle makes it an excellent target for cell therapy. However, the potential of muscle tissu … rogenitor cells, each with its own advantages and disadvantages. Most recently, mesoangioblasts and pericytes have been pursued for muscle cell therapy, leading to a handful of preclinical studies and a clinical trial. The current status of (pre)clinical work for the most common forms of MD illustrates the existing challenges and bottlenecks. Besides the in …

Role of TGF-Beta1/SMAD2/3 Pathway in Retinal Outer Deep Vascular Plexus and Photoreceptor Damage in Rat 50/10 Oxygen-Induced Retinopathy.

In retinopathy of prematurity (ROP), outer deep vascular plexus (oDVP) was the emerging field, and the mechanisms of photoreceptor dysfunction remained to be explored. ODVP and photoreceptors were related, with oDVP being part of the supplier of oxygen and nutrients to photoreceptors, while their possible relationship in ROP was not clear. TGF-beta1 has been reported indispensable in oDVP development and altered in ROP patients and animal models. We hypothesized that the TGF-beta1 alteration in rat 50/10 oxygen-induced retinopathy (OIR) model contributed to oDVP malformation and exerted conseq

Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis.

OBJECTIVE: The autologous stromal vascular fraction (SVF) from adipose tissue is an alternative to cultured adipose-derived stem cells for use in regenerative medicine and represents a promising therapy for vasculopathy and hand disability in systemic sclerosis (SSc). However, the bioactivity of autologous SVF is not documented in this disease context. This study aimed to compare the molecular and functional profiles of the SVF-based medicinal product obtained from SSc and healthy subjects. METHODS: Good manufacturing practice (GMP)-grade SVF from 24 patients with SSc and 12 healthy donors (H

CD160 Expression in Retinal Vessels Is Associated With Retinal Neovascular Diseases.

PURPOSE: Anti-angiogenic agents stand first in the treatment of neovascular diseases of the retina. CD160 appeared in several experimental studies as a marker of activated endothelial cells, suggesting it could represent a promising target for novel anti-angiogenic therapies. The aim of the present study was to assess the distribution of CD160 in the human eye, and to search for a possible correlation with retinal neovascular diseases. METHODS: The physiological distribution of CD160 in the normal eye was assessed with immunolabeling in 10 human donor eyes. Then, in a retrospective cohort of

Review: Relationship of type 2 diabetes to human brain pathology.

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT),

Zic Family Proteins in Emerging Biomedical Studies.

Zic family proteins have been investigated in various biomedical studies. Here we summarize the contact points between Zic proteins and rece … alies, but also controls maturation of the blood-brain barrier. Zic1 is also expressed in the brain pericytes possessing stem cell properties that control the blood-brain barrier activity and capillary hemodynamic responses. The possible involvement of Zic proteins in neuropsychiatric disorders has been indicated by the analyses of mutant mice behaviors. Zi …

Astrocyte disruption of neurovascular communication is linked to cortical damage in an animal model of multiple sclerosis.

To elucidate mechanisms contributing to cortical pathology in multiple sclerosis (MS), we investigated neurovascular aberrations, in particular the association of astrocytes with cortical neurons and blood vessels, in mice induced with experimental autoimmune encephalomyelitis (EAE). Blood-brain barrier (BBB) dysfunction was evident by leakage of the tracer sodium fluorescein, along with reduced expression of claudin-5 by endothelial cells and desmin by pericytes. Immunohistological and ultrastructural analyses revealed detachment of the astroglial cell bodies from the blood vessels and loss o…