scholarly journals Aged blood inhibits hippocampal neurogenesis and activates microglia through VCAM1 at the blood-brain barrier

2018 ◽  
Author(s):  
Hanadie Yousef ◽  
Cathrin J Czupalla ◽  
Davis Lee ◽  
Ashley Burke ◽  
Michelle Chen ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Immune Cell ◽  
Hippocampal Neurogenesis ◽  
Negative Regulator ◽  
Brain Barrier ◽  
Soluble Form ◽  
Aged Mouse ◽  
Genetic Ablation ◽  
Blood Brain ◽  
Age Related

AbstractAn aged circulatory environment can promote brain dysfunction and we hypothesized that the blood-brain barrier (BBB) mediates at least some of these effects. We observe brain endothelial cells (BECs) in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of Vascular Cell Adhesion Molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions. Concomitantly, the shed, soluble form of VCAM1 is prominently increased in the aged circulation of humans and mice, and aged plasma is sufficient to increase VCAM1 expression in cultured BECs and young mouse hippocampi. Systemic anti-VCAM1 antibody or genetic ablation of VCAM1 in BECs counteracts the detrimental effects of aged plasma on young brains and reverses aging aspects in old mouse brains. Thus, VCAM1 is a negative regulator of adult neurogenesis and inducer of microglial reactivity, establishing VCAM1 and the luminal side of the BBB as possible targets to treat age-related neurodegeneration.

scholarly journals Blood Brain Barrier Breakdown Following Topical Aldara Treatment

2020 ◽  
Author(s):  
Maria Suessmilch ◽  
Julie-Myrtille Bourgognon ◽  
Jonathan Cavanagh
Keyword(s):  
Blood Brain Barrier ◽  
Topical Application ◽  
Immune Cell ◽  
Hippocampal Neurogenesis ◽  
The Body ◽  
Brain Inflammation ◽  
Brain Barrier ◽  
Type I ◽  
Blood Brain ◽  
The Brain

Brain inflammation markers are present in several psychiatric and neurodegenerative disorders like major depressive disorder, Alzheimers disease and schizophrenia. Inflammation is also linked to sickness behaviour (social withdrawal, decreased appetite, impaired concentration, irritability), a mechanism by which the body redirects its resources to fight infection and encourage wound healing. The topical application of Aldara triggers systemic type I and II interferon and pro-inflammatory cytokine production, immune cell infiltration into the skin and hyperkeratosis and has been used as a model of psoriasis since 2009(1). We have recently reported that Imiquimod, the active component of Aldara, can enter the brain within 4 hours of topical application(2) and induces a transcriptional interferon and chemokine response in the brain, along with the infiltration of immune cells, a reduction in hippocampal neurogenesis and a reduction in burrowing behaviour(3). To allow us to understand the mechanisms of immune cell entry into the brain following topical Aldara treatment, we investigated blood brain barrier (BBB) integrity using a number of experimental techniques.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

The complexity of the blood-brain barrier and the concept of age-related brain targeting: challenges and potential of novel solid lipid-based formulations

2021 ◽  
Author(s):  
Federica Sommonte ◽  
Ilaria Arduino ◽  
Giuseppe Francesco Racaniello ◽  
Antonio Lopalco ◽  
Angela Assunta Lopedota ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Solid Lipid ◽  
Blood Brain ◽  
Age Related

Age-Related Changes in Blood-Brain Barrier ( BBB )

1990 ◽  
pp. 701-703
Author(s):  
Masaki Ueno ◽  
Hironobu Naiki ◽  
Ichiro Akiguchi ◽  
Toshio Kawamata ◽  
Yasuhisa Fujibayashi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Age Related ◽  
Age Related Changes

scholarly journals Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood-brain barrier

2017 ◽  
Vol 89 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Jonathan I Spencer ◽  
Jack S Bell ◽  
Gabriele C DeLuca
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
Neurological Diseases ◽  
Specific Immune Response ◽  
Brain Barrier ◽  
Vascular Pathology ◽  
Current Evidence ◽  
Blood Brain

Blood-brain barrier (BBB) disruption has long been recognised as an important early feature of multiple sclerosis (MS) pathology. Traditionally, this has been seen as a by-product of the myelin-specific immune response. Here, we consider whether vascular changes instead play a central role in disease pathogenesis, rather than representing a secondary effect of neuroinflammation or neurodegeneration. Importantly, this is not necessarily mutually exclusive from current hypotheses. Vascular pathology in a genetically predisposed individual, influenced by environmental factors such as pathogens, hypovitaminosis D and smoking, may be a critical initiator of a series of events including hypoxia, protein deposition and immune cell egress that allows the development of a CNS-specific immune response and the classical pathological and clinical hallmarks of disease. We review the changes that occur in BBB function and cerebral perfusion in patients with MS and highlight genetic and environmental risk factors that, in addition to modulating immune function, may also converge to act on the vasculature. Further context is provided by contrasting these changes with other neurological diseases in which there is also BBB malfunction, and highlighting current disease-modifying therapies that may also have an effect on the BBB. Indeed, in reframing current evidence in this model, the vasculature could become an important therapeutic target in MS.

scholarly journals Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment

2019 ◽  
Vol 11 ◽  
pp. 117957351984065 ◽  
Author(s):  
Divine C Nwafor ◽  
Allison L Brichacek ◽  
Afroz S Mohammad ◽  
Jessica Griffith ◽  
Brandon P Lucke-Wold ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
The United States ◽  
Brain Barrier ◽  
Blood Brain ◽  
Systemic Inflammatory Disease ◽  
Sepsis Survivors ◽  
The Brain

Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB’s role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.

scholarly journals miR‐195 reduces age‐related blood–brain barrier leakage caused by thrombospondin‐1‐mediated selective autophagy

Aging Cell ◽  
2020 ◽  
Vol 19 (11) ◽  
Author(s):  
Chien‐Yuan Chen ◽  
Yung‐Mei Chao ◽  
Hsiu‐Fen Lin ◽  
Chao‐Jung Chen ◽  
Cheng‐Sheng Chen ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Selective Autophagy ◽  
Blood Brain ◽  
Age Related ◽  
Thrombospondin 1

scholarly journals Fgfbp1 promotes blood-brain barrier development by regulating collagen IV deposition and maintaining Wnt/β-catenin signaling

Development ◽  
2020 ◽  
Vol 147 (16) ◽  
pp. dev185140
Author(s):  
Azzurra Cottarelli ◽  
Monica Corada ◽  
Galina V. Beznoussenko ◽  
Alexander A. Mironov ◽  
Maria A. Globisch ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Blood Brain Barrier ◽  
Collagen Iv ◽  
Cell Junctions ◽  
Brain Barrier ◽  
Extracellular Matrix Protein ◽  
Genetic Ablation ◽  
Vascular Basement Membrane ◽  
Blood Brain ◽  
Mouse Brain Endothelial Cells

ABSTRACTCentral nervous system (CNS) blood vessels contain a functional blood-brain barrier (BBB) that is necessary for neuronal survival and activity. Although Wnt/β-catenin signaling is essential for BBB development, its downstream targets within the neurovasculature remain poorly understood. To identify targets of Wnt/β-catenin signaling underlying BBB maturation, we performed a microarray analysis that identified Fgfbp1 as a novel Wnt/β-catenin-regulated gene in mouse brain endothelial cells (mBECs). Fgfbp1 is expressed in the CNS endothelium and secreted into the vascular basement membrane during BBB formation. Endothelial genetic ablation of Fgfbp1 results in transient hypervascularization but delays BBB maturation in specific CNS regions, as evidenced by both upregulation of Plvap and increased tracer leakage across the neurovasculature due to reduced Wnt/β-catenin activity. In addition, collagen IV deposition in the vascular basement membrane is reduced in mutant mice, leading to defective endothelial cell-pericyte interactions. Fgfbp1 is required cell-autonomously in mBECs to concentrate Wnt ligands near cell junctions and promote maturation of their barrier properties in vitro. Thus, Fgfbp1 is a crucial extracellular matrix protein during BBB maturation that regulates cell-cell interactions and Wnt/β-catenin activity.

Current Updates on the Regulation of Beta-Secretase Movement as a Potential Restorative Focus for Management of Alzheimer's Disease

2019 ◽  
Vol 26 (8) ◽  
pp. 579-587 ◽  
Author(s):  
Syed Sayeed Ahmad ◽  
Mohammad Amjad Kamal
Keyword(s):  
Blood Brain Barrier ◽  
Recent Decade ◽  
High Rate ◽  
Brain Barrier ◽  
Blood Brain ◽  
Age Related ◽  
Beta Secretase ◽  
Influx Transport ◽  
Clearance Receptor ◽  
The Brain

The most recent decade was described by a developing awareness about the seriousness of dementia in the field of age-related people. Among the dementias, Alzheimer's assumes a plentiful role as a result of its amazingly high rate and casualty. A few pharmacological procedures have been attempted yet at the same time now, Alzheimer continues being an untreatable malady. The collection of Aβ in the brain is an early poisonous occasion in the pathogenesis of Alzheimer's disease, which is the most widely recognized type of dementia correlated with plaques and tangles within the brain. However, the mechanism of the intraneuronal direction of BACE1 is poorly understood. AD is caused by mutations in one of the genes that encoding APP, presenilins 1 and 2. Most of the mutations in these genes increase Aβ42 production. Numerous receptors are associated with initiating Aβ transport and clearance. Among them, RAGE is an influx transport receptor that binds soluble Aβ and mediates pathophysiological cellular responses. RAGE additionally intervenes the vehicle of plasma Aβ over the blood-brain barrier. LRP-1 functions as a clearance receptor for Aβ at the blood-brain barrier. The regulation of beta-secretase movement is being explored as a potential restorative focus for treating AD.

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