Role of ginseng in the neurovascular unit of neuroinflammatory diseases focused on the blood-brain barrier

The blood–brain barrier (BBB) is a highly specialized neurovascular unit that protects the brain from potentially harmful substances. In addition, the BBB also engages in the exchange of essential nutrients between the vasculature and brain parenchyma, which is critical for brain homeostasis. Brain diseases, including neurological disorders and cerebrovascular diseases, are often associated with disrupted BBB integrity, evidenced by increased permeability. Therefore, defining the mechanisms underlying the regulation of BBB integrity is crucial for the development of novel therapeutics targeting brain diseases. MicroRNAs (miRNA), a type of small non-coding RNAs, are emerging as an important regulator of BBB integrity. Here we review recent developments related to the role of miRNAs in regulating BBB integrity.

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Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke

AJP Cell Physiology ◽

10.1152/ajpcell.00136.2018 ◽

2019 ◽

Vol 316 (2) ◽

pp. C135-C153 ◽

Cited By ~ 69

Author(s):

Changjun Yang ◽

Kimberly E. Hawkins ◽

Sylvain Doré ◽

Eduardo Candelario-Jalil

Keyword(s):

Ischemic Stroke ◽

Blood Brain Barrier ◽

Molecular Mechanisms ◽

Nitrosative Stress ◽

Current Knowledge ◽

Neurovascular Unit ◽

Neurological Dysfunction ◽

Brain Barrier ◽

Blood Brain

As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junction integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principal mediators and molecular mechanisms involved in BBB disruption is critical for the development of novel therapeutics to treat ischemic stroke. This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke. Specifically, we provide an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.

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The treatment of brain metastasis from breast cancer, role of blood-brain barrier disruption and early experience with trastuzumab

Therapy ◽

10.1586/14750708.3.1.97 ◽

2006 ◽

Vol 3 (1) ◽

pp. 97-112 ◽

Cited By ~ 2

Author(s):

Rose Marie Tyson ◽

Dale F Kraemer ◽

Matthew A Hunt ◽

Leslie L Muldoon ◽

Peter Orbay ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Blood Brain Barrier ◽

Early Experience ◽

Brain Barrier ◽

Barrier Disruption ◽

Blood Brain Barrier Disruption ◽

Blood Brain ◽

Brain Barrier Disruption

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THE ROLE OF INTRATHECAL IMMUNOGLOBULIN G SYNTHESIS AND BLOOD-BRAIN BARRIER PERMEABILITY STATE IN THE GENESIS OF RESISTANT FORMS OF EPILEPSY IN CHILDREN

10.26226/morressier.57d034d1d462b802923830d5 ◽

2016 ◽

Author(s):

Stanislav YEVTUSHENKO

Keyword(s):

Blood Brain Barrier ◽

Immunoglobulin G ◽

Brain Barrier ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability ◽

Permeability State

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Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527315666160202125304 ◽

2016 ◽

Vol 15 (3) ◽

pp. 301-309 ◽

Cited By ~ 3

Author(s):

Alexander L. Rusanov ◽

Natalia G. Luzgina ◽

George E. Barreto ◽

Gjumrakch Aliev

Keyword(s):

Cell Culture ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Cns Disorders ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability

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Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

Journal of Neuroinflammation ◽

10.1186/s12974-021-02145-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Sarinnapha M. Vasunilashorn ◽

◽

Long H. Ngo ◽

Simon T. Dillon ◽

Tamara G. Fong ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Blood Brain Barrier ◽

Plasma Levels ◽

Inflammatory Markers ◽

Brain Barrier ◽

Markers Of Inflammation ◽

Blood Brain ◽

Csf Levels ◽

The Relationship

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

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Screening for Interacting Proteins with Peptide Biomarker of Blood–Brain Barrier Alteration under Inflammatory Conditions

International Journal of Molecular Sciences ◽

10.3390/ijms22094725 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4725

Author(s):

Karina Vargas-Sanchez ◽

Monica Losada-Barragán ◽

Maria Mogilevskaya ◽

Susana Novoa-Herrán ◽

Yehidi Medina ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Neurovascular Unit ◽

Specific Interaction ◽

Brain Barrier ◽

Mass Spectrometry Analysis ◽

Peptide Ligand ◽

Inflammatory Conditions ◽

Blood Brain ◽

Potential Biomarker

Neurodegenerative diseases are characterized by increased permeability of the blood–brain barrier (BBB) due to alterations in cellular and structural components of the neurovascular unit, particularly in association with neuroinflammation. A previous screening study of peptide ligands to identify molecular alterations of the BBB in neuroinflammation by phage-display, revealed that phage clone 88 presented specific binding affinity to endothelial cells under inflammatory conditions in vivo and in vitro. Here, we aimed to identify the possible target receptor of the peptide ligand 88 expressed under inflammatory conditions. A cross-link test between phage-peptide-88 with IL-1β-stimulated human hCMEC cells, followed by mass spectrometry analysis, was used to identify the target of peptide-88. We modeled the epitope–receptor molecular interaction between peptide-88 and its target by using docking simulations. Three proteins were selected as potential target candidates and tested in enzyme-linked immunosorbent assays with peptide-88: fibronectin, laminin subunit α5 and laminin subunit β-1. Among them, only laminin subunit β-1 presented measurable interaction with peptide-88. Peptide-88 showed specific interaction with laminin subunit β-1, highlighting its importance as a potential biomarker of the laminin changes that may occur at the BBB endothelial cells under pathological inflammation conditions.

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