scholarly journals Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

2019 ◽  
Vol 20 (21) ◽  
pp. 5393 ◽  
Author(s):  
Herold ◽  
Schroten ◽  
Schwerk
Keyword(s):  
Blood Brain Barrier ◽  
Virulence Factors ◽  
Host Cells ◽  
Brain Barrier ◽  
Host Cell Signaling ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Difference ◽  
Multiple Pathogens ◽  
The Brain

Infections of the central nervous system (CNS) are still a major cause of morbidity and mortality worldwide. Traversal of the barriers protecting the brain by pathogens is a prerequisite for the development of meningitis. Bacteria have developed a variety of different strategies to cross these barriers and reach the CNS. To this end, they use a variety of different virulence factors that enable them to attach to and traverse these barriers. These virulence factors mediate adhesion to and invasion into host cells, intracellular survival, induction of host cell signaling and inflammatory response, and affect barrier function. While some of these mechanisms differ, others are shared by multiple pathogens. Further understanding of these processes, with special emphasis on the difference between the blood–brain barrier and the blood–cerebrospinal fluid barrier, as well as virulence factors used by the pathogens, is still needed.

scholarly journals Blood-brain barrier behavior during temporary concussion

1960 ◽  
Vol 198 (6) ◽  
pp. 1296-1298 ◽  
Author(s):  
Benedict Cassen ◽  
Richard Neff
Keyword(s):  
Central Nervous System ◽  
Blood Brain Barrier ◽  
Normal Activity ◽  
Brain Barrier ◽  
Electrolyte Balance ◽  
Barrier Membranes ◽  
Phosphate Ions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

Experimental evidence is obtained that, coincident with a state of not too severe concussion, the blood-brain barrier system becomes more permeable to phosphate ions. The permeability returns to normal when the animal recovers and shows normal activity. Arguments are presented in favor of the hypothesis that dysfunction of the central nervous system during concussion is related to a disturbed electrolyte balance in the fluids of the brain caused by a piezochemical disturbance of the blood-brain barrier membranes (presumably the astropods of the astrocytic cells).

scholarly journals Photostimulation of Extravasation of Beta-Amyloid through the Model of Blood-Brain Barrier

Electronics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1056
Author(s):  
Ekaterina Zinchenko ◽  
Maria Klimova ◽  
Aysel Mamedova ◽  
Ilana Agranovich ◽  
Inna Blokhina ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Beta Amyloid ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Cervical Lymph Nodes ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Vitro Model ◽  
The Brain

Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system.

scholarly journals Transport of D-Glucose and 2-Fluorodeoxyglucose across the Blood-Brain Barrier in Humans

1996 ◽  
Vol 16 (4) ◽  
pp. 659-666 ◽  
Author(s):  
Steen G. Hasselbalch ◽  
Gitte M. Knudsen ◽  
Søren Holm ◽  
L. Pinborg Hageman ◽  
Brunella Capaldo ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Initial Distribution ◽  
Brain Barrier ◽  
Transport Parameters ◽  
Indicator Method ◽  
Blood Brain ◽  
The Difference ◽  
Regional Cerebral Glucose Metabolism ◽  
The Brain

The deoxyglucose method for calculation of regional cerebral glucose metabolism by PET using 18F-2-fluoro-2-deoxy-d-glucose (FDG) requires knowledge of the lumped constant, which corrects for differences in the blood–brain barrier (BBB) transport and phosphorylation of FDG and glucose. The BBB transport rates of FDG and glucose have not previously been determined in humans. In the present study these transport rates were measured with the intravenous double-indicator method in 24 healthy subjects during normoglycemia (5.2 ± 0.7 m M). Nine subjects were restudied during moderate hypoglycemia (3.4 ± 0.4 m M) and five subjects were studied once during hyperglycemia (15.0 ± 0.7 m M). The global ratio between the unidirectional clearances of FDG and glucose (K1*/K1) was similar in normoglycemia (1.48 ± 0.22), moderate hypoglycemia (1.41 ± 0.23), and hyperglycemia (1.44 ± 0.20). This ratio is comparable to what has been obtained in rats. We argue that the global ratio is constant throughout the brain and may be applied for the regional determination of LC. We also determined the transport parameters of the two hexoses from brain back to blood and, assuming symmetrical transport across the BBB, we found evidence of a larger initial distribution volume of FDG in brain (0.329 ± 0.236) as compared with that of glucose (0.162 ± 0.098, p < 0.005). The difference can be explained by the very short experimental time, in which FDG may distribute both intra- and extracellularly, whereas glucose remains in a volume comparable to the interstitial fluid of the brain.

scholarly journals Tembusu Virus entering the central nervous system caused nonsuppurative encephalitis without disrupting the blood-brain barrier

2021 ◽  
Author(s):  
Sheng Yang ◽  
Yufei Huang ◽  
Yonghong Shi ◽  
Xuebing Bai ◽  
Ping Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Neurological Symptoms ◽  
Brain Barrier ◽  
Poultry Industry ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Tembusu Virus ◽  
The Brain

Tembusu Virus (TMUV) is an emerging and re-emerging zoonotic pathogen that adversely affects poultry industry in recent years. TMUV disease is characterized by nonsuppurative encephalitis in ducklings. The duckling infection model was established to study the mechanism of TMUV crossing the blood-brain barrier (BBB) into the central nervous system (CNS). Here, we showed that no obvious clinical symptoms and enhancement of BBB permeability occurred at the early stage of infection (3∼5 dpi). While simultaneously virus particles were observed by transmission electron microscopy in the brain, inducing the accumulation of inflammatory cytokines. Neurological symptoms and disruption of BBB appeared at the intermediate stage of infection (7∼9 dpi). It was confirmed that TMUV could survive and propagate in brain microvascular endothelial cells (BMECs), but did not affect the permeability of BBB in vivo and in vitro at an early date. In conclusion, TMUV enters the CNS then causes encephalitis, and finally destruct the BBB, which may be due to the direct effect of TMUV on BMECs and the subsequent response of “inflammatory storm”. IMPORTANCE The TMUV disease has caused huge losses to the poultry industry in Asia, which is potentially harmful to public health. Neurological symptoms and their sequelae are the main characters of this disease. However, the mechanism of how this virus enters the brain and causes encephalitis is unclear. In this study, we confirmed that the virus entered the CNS and then massively destroyed BBB and the BBB damage was closely associated with the subsequent outbreak of inflammation. TMUV may enter the CNS through the transcellular and “Trojan horse” pathways. These findings can fill the knowledge gap in the pathogenesis of TMUV-infected poultry and be benefit for the treatment of TMUV disease. What’s more, TMUV is a representative to study the infection of avian flavivirus. Therefore, our studies have significances both for understanding of the full scope of mechanisms of TMUV and other flavivirus infection, and conceivably, for therapeutics.

Iodide and thiocyanate efflux from brain following injection into rat caudate nucleus

1978 ◽  
Vol 235 (4) ◽  
pp. F331-F337 ◽  
Author(s):  
H. F. Cserr ◽  
B. J. Berman
Keyword(s):  
Caudate Nucleus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Common Mechanism ◽  
Efflux System ◽  
Guide Cannula ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Loading Estimates ◽  
The Brain

Mechanisms and pathways of 125I and 35SCN efflux from the brain were investigated in anesthetized rats. Tracers were injected into the caudate nucleus through a guide cannula implanted 1 wk previously and concentrations of isotope in brain and cerebrospinal fluid (CSF) were determined at various times after injection. 125I clearance from the brain followed a single exponential curve. In control rats 36.2% of the 125I remained in the brain 30 min after injection and 60.4% in rats pretreated with perchlorate. Comparable values for 35SCN were 25.8% in control rats, 41.0% with perchlorate, and 39.7% with iodide loading. Estimates of 125I and 35SCN effluxes from the brain via the blood-brain barrier and CSF pathways suggest that greater than 95% of efflux crosses the blood-brain barrier. These results indicate that 1)iodide and thiocyanate are transported across the blood-brain barrier by a common mechanism, and 2) this efflux system is an important factor in the control of the distributions of iodide and thiocyanate in the central nervous system.

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases

2020 ◽  
Vol 17 (5) ◽  
pp. 375-386 ◽  
Author(s):  
Behrang Shiri Varnamkhasti ◽  
Samira Jafari ◽  
Fereshteh Taghavi ◽  
Loghman Alaei ◽  
Zhila Izadi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Disorders ◽  
Blood Brain ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
The Central Nervous System ◽  
Low Cytotoxicity ◽  
The Brain

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.

scholarly journals PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 72 ◽  
Author(s):  
Gina P. Hoyos-Ceballos ◽  
Barbara Ruozi ◽  
Ilaria Ottonelli ◽  
Federica Da Ros ◽  
Maria Angela Vandelli ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Glycolic Acid ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Proof Of Concept ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Research Challenge ◽  
The Brain

The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.

scholarly journals ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System

2008 ◽  
Vol 82 (8) ◽  
pp. 4164-4168 ◽  
Author(s):  
Jianfeng Dai ◽  
Penghua Wang ◽  
Fengwei Bai ◽  
Terrence Town ◽  
Erol Fikrig
Keyword(s):  
West Nile Virus ◽  
Blood Brain Barrier ◽  
Viral Encephalitis ◽  
Neuronal Damage ◽  
Brain Barrier ◽  
Lower Viral Load ◽  
West Nile ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Determining how West Nile virus crosses the blood-brain barrier is critical to understanding the pathogenesis of encephalitis. Here, we show that ICAM-1−/− mice are more resistant than control animals to lethal West Nile encephalitis. ICAM-1−/− mice have a lower viral load, reduced leukocyte infiltration, and diminished neuronal damage in the brain compared to control animals. This is associated with decreased blood-brain barrier leakage after viral infection. These data suggest that ICAM-1 plays an important role in West Nile virus neuroinvasion and that targeting ICAM-1 signaling may help control viral encephalitis.

scholarly journals Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Oxana Semyachkina-Glushkovskaya ◽  
Ivan Fedosov ◽  
Alexander Shirokov ◽  
Elena Vodovozova ◽  
Anna Alekseeva ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Significant Contribution ◽  
Brain Barrier ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
Effective Delivery ◽  
The Central Nervous System ◽  
Free Generation ◽  
Lymphatic Delivery ◽  
The Brain

Abstract The blood-brain barrier (BBB) has a significant contribution to the protection of the central nervous system (CNS). However, it also limits the brain drug delivery and thereby complicates the treatment of CNS diseases. The development of safe methods for an effective delivery of medications and nanocarriers to the brain can be a revolutionary step in the overcoming this limitation. Here, we report the unique properties of the lymphatic system to deliver tracers and liposomes to the brain meninges, brain tissues, and glioma in rats. Using a quantum-dot-based 1267 nm laser (for photosensitizer-free generation of singlet oxygen), we clearly demonstrate photostimulation of lymphatic delivery of liposomes to glioma as well as lymphatic clearance of liposomes from the brain. These pilot findings open promising perspectives for photomodulation of lymphatic delivery of drugs and nanocarriers to the brain pathology bypassing the BBB. The lymphatic “smart” delivery of liposomes with antitumor drugs in the new brain tumor branches might be a breakthrough strategy for the therapy of gliomas.

scholarly journals Blood-brain barrier-restricted translocation of Toxoplasma gondii from cortical capillaries

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gabriela C Olivera ◽  
Emily C Ross ◽  
Christiane Peuckert ◽  
Antonio Barragan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Toxoplasma Gondii ◽  
Blood Brain Barrier ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Cortical Capillaries ◽  
The Brain

The cellular barriers of the central nervous system proficiently protect the brain parenchyma from infectious insults. Yet, the single-celled parasite Toxoplasma gondii commonly causes latent cerebral infection in humans and other vertebrates. Here, we addressed the role of the cerebral vasculature in the passage of T. gondii to the brain parenchyma. Shortly after inoculation in mice, parasites mainly localized to cortical capillaries, in preference over post-capillary venules, cortical arterioles or meningeal and choroidal vessels. Early invasion to the parenchyma (days 1-5) occurred in absence of a measurable increase in blood-brain barrier (BBB) permeability, perivascular leukocyte cuffs or hemorrhage. However, sparse focalized permeability elevations were detected adjacently to replicative parasite foci. Further, T. gondii triggered inflammatory responses in cortical microvessels and endothelium. Pro- and anti-inflammatory treatments of mice with LPS and hydrocortisone, respectively, impacted BBB permeability and parasite loads in the brain parenchyma. Finally, pharmacological inhibition or Cre/loxP conditional knockout of endothelial focal adhesion kinase (FAK), a BBB intercellular junction regulator, facilitated parasite translocation to the brain parenchyma. The data reveal that the initial passage of T. gondii to the central nervous system occurs principally across cortical capillaries. The integrity of the microvascular BBB restricts parasite transit, which conversely is exacerbated by the inflammatory response.

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