scholarly journals The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yiwei Wang ◽  
Huanhuan Sha ◽  
Leting Zhou ◽  
Yinan Chen ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Mast Cell ◽  
Blood Brain Barrier ◽  
Microglial Activation ◽  
Brain Barrier ◽  
Brain Disorders ◽  
Barrier Dysfunction ◽  
Cns Inflammation ◽  
Lps Challenge ◽  
Blood Brain ◽  
The Brain

Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.

Accessing the Blood-Brain Barrier to Treat Brain Disorders

2019 ◽  
Vol 9 (3) ◽  
pp. 198-209
Author(s):  
M. Sureshkumar ◽  
A. Pandian
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Low Molecular Weight ◽  
Brain Disorders ◽  
Permeable Membrane ◽  
Drug Molecules ◽  
Blood Brain ◽  
Therapeutic Molecules ◽  
Pass Through ◽  
The Brain

: Crossing the blood-brain barrier (BBB) and treating brain disorders by delivering therapeutic agents to specific regions of the brain is a challenge. The BBB, naturally evolved, protective physiological barrier acts as a selective permeable membrane in such a way that it allows only nonionic molecules and molecules of low molecular weight to pass through. Treating brain tumor has become a great challenge as the drug molecules of larger size are not able to cross the BBB and reach the target site. The incompetence of techniques for brain-specific delivery of therapeutic molecules has led researchers to increasingly explore the diagnosis and treatment of disorders incurable with present techniques. This article is to discuss the various techniques or methods to deliver drugs to the brain crossing the BBB.

scholarly journals Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Francisco De Jesús Andino ◽  
Letitia Jones ◽  
Sanjay B. Maggirwar ◽  
Jacques Robert
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Frog Virus 3 ◽  
Frog Virus ◽  
Blood Brain ◽  
The Brain

scholarly journals The Dual Role of Microglia in Blood-Brain Barrier Dysfunction after Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1237-1249 ◽  
Author(s):  
Ruiqing Kang ◽  
Marcin Gamdzyk ◽  
Cameron Lenahan ◽  
Jiping Tang ◽  
Sheng Tan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Vital Role ◽  
Dual Role ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
M2 Microglia ◽  
The Brain

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

Microglial activation and increased synthesis of complement component C1q precedes blood–brain barrier dysfunction in rats

2004 ◽  
Vol 40 (10) ◽  
pp. 709-716 ◽  
Author(s):  
Nicholas J Lynch ◽  
Colin L Willis ◽  
Christopher C Nolan ◽  
Silke Roscher ◽  
Maxine J Fowler ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Microglial Activation ◽  
Complement Component ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

scholarly journals Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

2016 ◽  
Vol 36 (9) ◽  
pp. 1481-1507 ◽  
Author(s):  
Ralf G Rempe ◽  
Anika MS Hartz ◽  
Björn Bauer
Keyword(s):  
Matrix Metalloproteinases ◽  
Blood Brain Barrier ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Cerebral Aneurysms ◽  
The Body ◽  
Brain Barrier ◽  
Brain Disorders ◽  
Blood Brain ◽  
The Brain

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders.

Cadmium-induced alterations in blood- brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat

1996 ◽  
Vol 15 (5) ◽  
pp. 400-405 ◽  
Author(s):  
Arti Shukla ◽  
Girja S Shukla ◽  
RC Srimal
Keyword(s):  
Glutathione Peroxidase ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Albino Rats ◽  
Barrier Dysfunction ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

1 Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt) in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels by 76% ( P < 0.05) and 165% ( P < 0.001) respec tively at 30 and 90 days of exposure compared to controls. 2 Cadmium increased blood - brain barrier permeability of fluoroscein dye (24%, P < 0.02) and the levels ofbrain microvessel malondialdehyde (31%, P<0.01) at 90 days of exposure. However, these parameters did not alter significantly at 30 days of exposure. 3 Increased activities of microvessel superoxide dismu tase (18%, P<0.02), glutathione peroxidase (20%, P<0.01) and catalase (28%, P<0.01) were observed at 30 days of exposure. 4 The continuation of the Cd treatment for 90 days decreased the levels of superoxide dismutase (30%, P<0.001), glutathione peroxidase (23%, P<0.005), catalase (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P < 0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and ceruloplas min (13%, P<0.05) in the microvessal preparation compared to controls. 5 It appears that Cd-induced blood-brian barrier dysfunction may be related to the depletion of microvessel antioxidant substances along with in crease in lipid peroxidation at 90 days of exposure.

scholarly journals Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain

2006 ◽  
Vol 290 (2) ◽  
pp. H732-H740 ◽  
Author(s):  
J. D. Huber ◽  
C. R. Campos ◽  
K. S. Mark ◽  
T. P. Davis
Keyword(s):  
Protein Expression ◽  
Blood Brain Barrier ◽  
Proinflammatory Cytokines ◽  
Inflammatory Pain ◽  
Microglial Activation ◽  
Brain Barrier ◽  
Cell Counts ◽  
Blood Brain ◽  
Junction Protein ◽  
The Brain

Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1–6 h); however, brain region-specific increases in microglial activation suggest a potential for a central-mediated response.

scholarly journals EXPERIMENTAL INTESTINAL DYSBIOSIS IN RATS INCREASES THE PERMEABILITY OF THE BLOOD-BRAIN BARRIER AND INDUCES NEUROINFLAMMATION

2019 ◽  
Vol 19 (1S) ◽  
pp. 104-105
Author(s):  
V G Sergeyev ◽  
T N Sergeyeva
Keyword(s):  
Blood Brain Barrier ◽  
Intestinal Barrier ◽  
Alpha Synuclein ◽  
Brain Barrier ◽  
Local Inflammation ◽  
Barrier Dysfunction ◽  
Cellular Mechanisms ◽  
Blood Brain ◽  
Intestinal Dysbiosis ◽  
The Brain

The mammalian intestinal microbiota consists of bacteria, fungi and viruses, including bacteriophages. This complex ecosystem has dynamic stability. It is assumed that changes in the composition of the microbiota can cause intestinal barrier dysfunction and the development of a number of pathologies, including neurodegenerative diseases accompanied by neuroinflammation. The molecular and cellular mechanisms underlying such a relationship remain poorly understood. We hypothesized that bacteriophages cause intestinal dysbiosis, increased intestinal permeability and local inflammation. Bacterial factors (endotoxins, zonulin-like proteins) and local inflammation products (cytokines, alpha-synuclein protein) can enter the circulation and increase the permeability of the blood-brain barrier (BBB), which will cause neuro-inflammation and damage to neurons. In this study, we observed an increase in BBB permeability and induction of neuroinflammation in the brain after rectal administration of a bacteriophage cocktail (Microgen, Russia). The permeability of the BBB was judged by the volume of the vital dye (Evans blue) emerging from the bloodstream into the brain parenchyma, and the development of the neuroinflammatory response by increasing the number of immunohistochemically stained microglial and astroglial cells.

scholarly journals Drug Delivery Challenges in Brain Disorders across the Blood–Brain Barrier: Novel Methods and Future Considerations for Improved Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1834
Author(s):  
Aneesha Achar ◽  
Rosemary Myers ◽  
Chaitali Ghosh
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Disorders ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Bioavailability ◽  
Unique Challenge ◽  
Blood Brain ◽  
Drug Interventions ◽  
The Brain

Due to the physiological and structural properties of the blood–brain barrier (BBB), the delivery of drugs to the brain poses a unique challenge in patients with central nervous system (CNS) disorders. Several strategies have been investigated to circumvent the barrier for CNS therapeutics such as in epilepsy, stroke, brain cancer and traumatic brain injury. In this review, we summarize current and novel routes of drug interventions, discuss pharmacokinetics and pharmacodynamics at the neurovascular interface, and propose additional factors that may influence drug delivery. At present, both technological and mechanistic tools are devised to assist in overcoming the BBB for more efficient and improved drug bioavailability in the treatment of clinically devastating brain disorders.

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