Phytomedicine, Год журнала: 2025, Номер unknown, С. 156646 - 156646
Опубликована: Март 1, 2025
Язык: Английский
Pharmaceutics, Год журнала: 2021, Номер 13(11), С. 1779 - 1779
Опубликована: Окт. 26, 2021
The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity vital to maintain homeostasis brain microenvironment by controlling passage substances regulating trafficking immune cells between blood brain. BBB primarily composed highly specialized microvascular endothelial cells. These cells' special features physiological properties are acquired maintained through concerted effort hemodynamic cellular cues from surrounding environment. This complex multicellular system, comprising cells, astrocytes, pericytes, neurons, known as neurovascular unit (NVU). strictly controls transport nutrients metabolites into parenchyma tightly regulated while limiting access potentially harmful via efflux transcytosis metabolic mechanisms. Not surprisingly, disruption has been associated with onset and/or progression major neurological disorders. Although association disease clear, its nature not always evident, specifically regard whether an impaired function results pathological condition or damage primary pathogenic factor prodromal disease. In either case, repairing could be viable option for treating reducing effects CNS this review, we describe structure in both healthy altered/diseased conditions. Additionally, provide overview potential therapeutic targets that leveraged restore concomitant treatment these
Язык: Английский
Процитировано
120
Nature Reviews Neurology, Год журнала: 2024, Номер 20(3), С. 162 - 182
Опубликована: Фев. 14, 2024
Язык: Английский
Процитировано
32
Journal of Advanced Research, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Endothelial cells (ECs) and pericytes (PCs) are crucial components of the vascular system, with ECs lining inner layer blood vessels PCs surrounding capillaries to regulate flow angiogenesis. Intercellular communication between is vital for formation, stability, function vessels. Various signaling pathways, such as endothelial growth factor/vascular factor receptor pathway platelet-derived factor-B/platelet-derived receptor-β pathway, play roles in PCs. Dysfunctional these associated various diseases, including central nervous system disorders, certain types cancers. review: This review aimed explore diverse formation reshaping focused on essential pathways that facilitate investigated how disruptions may contribute disease. Additionally, explored potential therapeutic targets, future research directions, innovative approaches, investigating impact EC-PCs novel systemic addressing resistance antiangiogenic drugs, developing medications enhance efficacy. Key scientific concepts Disordered EC-PC intercellular plays a role abnormal vessel thus contributing progression diseases development drugs. Therefore, studies interactions have high clinical relevance.
Язык: Английский
Процитировано
20
Alzheimer s & Dementia, Год журнала: 2025, Номер unknown
Опубликована: Янв. 14, 2025
Abstract INTRODUCTION Interferon‐induced transmembrane protein 3 (IFITM3) modulates γ‐secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β (Aβ) production, its cell‐specific effect on AD remains unclear. METHODS Single nucleus RNA sequencing (snRNA‐seq) was used to assess expression. Adeno‐associated virus‐BI30 (AAV‐BI30) injected reduce expression the cerebrovascular endothelial cells (CVECs). The effects phenotypes and mice were examined through behavioral tests, two‐photon imaging, flow cytometry, Western blot, immunohistochemistry, quantitative polymerase chain reaction assay (qPCR). RESULTS increased CVECs of patients with AD. Overexpression primary enhanced Aβ generation regulating beta‐site APP cleaving enzyme 1 (BACE1) γ‐secretase. further expression, creating a vicious cycle. Knockdown decreased accumulation within walls, reduced Alzheimer's‐related pathology, improved cognitive performance transgenic mice. DISCUSSION alleviates pathology impairment. Targeting holds promise for treatment. Highlights ( ) (CVECs) Cerebrovascular regulates deposits improves impairments could be potential target treatment
Язык: Английский
Процитировано
2
Cells, Год журнала: 2022, Номер 11(5), С. 813 - 813
Опубликована: Фев. 25, 2022
The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between neural cells and blood vessels in human brain, focused mainly on brain gray matter. major components of NVU are neurons, astrocytes (astroglia), microvessels, pericytes, microglia. In addition, we believe oligodendrocytes should also be included as an indispensable component white Of all these components, particular have attracted interest researchers because their unique anatomical location; interposed neurons microvessels brain. Their location suggests might regulate cerebral flow (CBF) response neuronal activity, so ensure adequate supply glucose oxygen meet metabolic demands neurons. fact, adult which accounts for only 2% entire body weight, consumes approximately 20–25% total amount consumed by whole body. needs continuous essential energy sources through CBF, there practically no stores or brain; both acute chronic cessation CBF can adversely affect functions. another important putative function elimination heat waste materials produced activity. Recent evidence play pivotal roles not supplying glucose, but fatty acids amino Loss astrocytic support expected lead malfunction whole, underlies numerous neurological disorders. this review, shall focus historical recent findings with regard contributions NVU.
Язык: Английский
Процитировано
54
Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. e1251232024 - e1251232024
Опубликована: Янв. 22, 2024
Increasing evidence has suggested a link between cerebrovascular disease and the cognitive impairment associated with Alzheimer's Disease. However, detailed descriptions of microvascular changes across brain regions how they relate to other more traditional pathology have been lacking. Additionally, efforts elucidate interplay cerebral function Disease progression are complicated by necessity probing deep-brain structures since early-stage typically involves hippocampal pathology. The purpose this study was examine in dynamics mouse model using cohorts that were age-matched wild-type controls. Data from both sexes included study. Super-resolution ultrasound localization microscopy revealed functional structural features throughout whole depth visualize quantify. We found decreases entorhinal flow velocity preceded derangements regional vascular density. Co-registered histological sectioning confirmed regionalized perfusion deficits seen on imaging, which co-localized amyloid beta plaque deposition. In addition providing global quantifications deep high local resolution, technology also permitted velocity-profile analysis individual vessels and, some cases, allowed for decoupling arterial venous contributions. These data suggest is an early pervasive feature may represent novel therapeutic target disease. Significance statement Studies impact difficulty imaging fidelity. demonstrate microscopy, super-resolution acoustic technique, capable cerebrovasculature entire at scale. This applied 5xFAD Disease, where it animals significant impairments cortex hippocampus compared age matched controls 3-month timepoint. Structural only observed 6-month-old timepoint, maintained function. findings occurs cascade.
Язык: Английский
Процитировано
12
Biology, Год журнала: 2024, Номер 13(2), С. 70 - 70
Опубликована: Янв. 23, 2024
Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative it contributes significantly to the global health burden. Recent research indicates a link between risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, endothelial dysfunction. Circulating progenitor cells (EPCs) are recruited into vessel wall maintain appropriate function, repair, angiogenesis. After attachment, EPCs differentiate mature (ECs). Like ECs, also susceptible CVRFs, metabolic chronic inflammation. Therefore, may have long-term effects on function ECs which differentiate, particularly in presence damage. However, CVRFs impaired has hardly been investigated. In this review, we aim consolidate existing knowledge development vascular endothelium, place context recent studies investigating consequences EPCs, discuss role Thus, gain comprehensive understanding mechanisms involved EPC deterioration relation address potential therapeutic interventions targeting promote function.
Язык: Английский
Процитировано
10
Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 13
Опубликована: Янв. 26, 2022
Alzheimer's disease (AD) is a neurodegenerative representing the most common type of dementia worldwide. The early diagnosis AD very difficult to achieve due its complexity and practically unknown etiology. Therefore, this one greatest challenges in field order develop an accurate therapy. Within different etiological hypotheses proposed for AD, we will focus on two-hit vascular hypothesis alterations occurring disease. According hypothesis, accumulation β-amyloid protein brain starts as consequence damage cerebral vasculature. Given that there are several angiogenic endothelial progenitor cells (EPCs) play key role repair processes, study EPCs may be relevant etiology perhaps biomarker and/or therapeutic target. This review focuses involvement dysfunction onset progression with special emphasis potential
Язык: Английский
Процитировано
33
Brain Pathology, Год журнала: 2023, Номер 33(6)
Опубликована: Май 9, 2023
Abstract Circulating C‐reactive protein (pCRP) concentrations rise dramatically during both acute (e.g., following stroke) or chronic infection and disease autoimmune conditions such as lupus), providing complement fixation through C1q binding. It is now known, that on exposure to the membranes of activated immune cells (and microvesicles platelets), damaged/dysfunctional tissue, it undergoes lysophosphocholine (LPC)‐phospholipase‐C‐dependent dissociation monomeric form (mCRP), concomitantly becoming biologically active. We review histological, immunohistochemical, morphological/topological studies post‐mortem brain tissue from individuals with neuroinflammatory disease, showing mCRP becomes stably distributed within parenchyma, resident in arterial intima lumen, being “released” damaged, hemorrhagic vessels into extracellular matrix. The possible de novo synthesis via neurons, endothelial cells, glia also considered. In vitro, vivo , human co‐localization analyses have linked neurovascular dysfunction, vascular activation resulting increased permeability, leakage, compromise blood barrier function, buildup toxic proteins including tau beta amyloid (Aβ), association capacity “manufacture” Aβ‐mCRP‐hybrid plaques, and, greater susceptibility neurodegeneration dementia. Recently, several CRP/mCRP systemic expression risk dementia mechanisms which this occurs are investigated here. unit mediates correct intramural periarterial drainage, evidence provided here suggests a critical impact elements could suggest its participation earliest stages dysfunction conclude further investigation warranted. discuss future therapeutic options aimed at inhibiting pCRP‐LPC mediated associated pathology, for example, compound 1,6‐bis‐PC, injected intravenously, prevented deposition damage, after temporary left anterior descending artery ligation myocardial infarction rat model.
Язык: Английский
Процитировано
17
The Journal of Nutritional Biochemistry, Год журнала: 2024, Номер 125, С. 109570 - 109570
Опубликована: Янв. 11, 2024
Язык: Английский
Процитировано
8