scholarly journals Macrophages Enforce the Blood Nerve Barrier

2019 ◽  
Author(s):  
Liza Malong ◽  
Ilaria Napoli ◽  
Ian J White ◽  
Salome Stierli ◽  
Alessandro Bossio ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Barrier Function ◽  
Cellular Composition ◽  
Complete Coverage ◽  
Therapeutic Delivery ◽  
The Central Nervous System ◽  
Low Levels ◽  
Cellular Components ◽  
Distinct Role

The specialised blood barriers of the nervous system are important for protecting the neural environment but can hinder therapeutic accessibility1,2. Studies in the central nervous system (CNS) have shown the importance of the cellular components of the neuro-vascular unit for blood-brain barrier (BBB) function. Whilst the endothelial cells (ECs) confer barrier function with specialised tight junctions (TJs) and low levels of transcytosis, pericytes and astrocytes provide complete coverage of the ECs and both deliver essential signals for the development and maintenance of the BBB3–9. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system (PNS) remains poorly defined10. Here, we show that the vascular unit in the PNS has a distinct cellular composition with only partial coverage of the BNB-forming ECs. Using a mouse model, in which barrier function can be controlled11, we show the BNB, while less tight than the BBB, is maintained by low levels of transcytosis and the TJs of the ECs, with opening of the barrier associated with increased transcytosis. Importantly, we find that while ECs of the PNS have higher transcytosis rates than those of the CNS, the barrier is reinforced by resident macrophages that specifically engulf leaked material. This identifies a distinct role for macrophages as an important component of the BNB acting to protect the PNS environment with implications for improving therapeutic delivery to this tissue.

Assembling the Emotions

2006 ◽  
Vol 32 ◽  
pp. 185-212 ◽  
Author(s):  
Vincent Bergeron ◽  
Mohan Matthen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cognitive Processing ◽  
Endogenous Depression ◽  
Adequate Account ◽  
The World ◽  
The Central Nervous System ◽  
Low Levels ◽  
Highly Correlated ◽  
Proper Account

Endogenous depression is highly correlated with low levels of serotonin in the central nervous system. Does this imply or suggest that this sort of depression just is this neurochemical deficit? Scorning such an inference, Antonio Damasio writes:If feeling happy or sad … corresponds in part to the cognitive modes under which your thoughts are operating, then the explanation also requires that the chemical acts on the circuits which generate and manipulate [such thoughts]. Which means that reducing depression to a statement about the availability of serotonin or norepinephrine in general- a popular statement in the days and age of Prozac- is unacceptably rude (1995, 161).Damasio's thought is that depression is essentially a modification of how we perceive the world, reason about it, and make decisions about how to act in it - in other words, that it is essentially cognitive. A reduced level of serotonin might cause the said modification, but no adequate account of depression would identify the malady with its cause. A proper account would minimally need to say how cognitive processing is affected by a reduced level of serotonin.

scholarly journals Murine Coronavirus Receptors Are Differentially Expressed in the Central Nervous System and Play Virus Strain-Dependent Roles in Neuronal Spread

2010 ◽  
Vol 84 (21) ◽  
pp. 11030-11044 ◽  
Author(s):  
Susan J. Bender ◽  
Judith M. Phillips ◽  
Erin P. Scott ◽  
Susan R. Weiss
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Hepatitis Virus ◽  
Cell Types ◽  
Cns Infection ◽  
The Central Nervous System ◽  
Coronavirus Infection ◽  
Low Levels

ABSTRACT Coronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infected in vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types, ceacam1a mRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels of ceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression of ceacam1a, primary neurons from wild-type and ceacam1a knockout mice were inoculated with MHV to determine the extent to which CEACAM1a-independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers of ceacam1a knockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for the ceacam1a-related genes ceacam2 and psg16 (bCEA), which encode proposed alternative MHV receptors, revealed low ceacam2 expression in microglia and oligodendrocytes and psg16 expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a-independent neuronal spread of JHM.SD remains unknown.

scholarly journals Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation

2021 ◽  
Vol 22 (12) ◽  
pp. 6259
Author(s):  
Amany Tawfik ◽  
Nehal M. Elsherbiny ◽  
Yusra Zaidi ◽  
Pragya Rajpurohit
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Barrier Function ◽  
Underlying Mechanism ◽  
Age Related Macular Degeneration ◽  
Barrier Dysfunction ◽  
Age Related ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Hyperhomocysteinemia (HHcy) is remarkably common among the aging population. The relation between HHcy and the development of neurodegenerative diseases, such as Alzheimer’s disease (AD) and eye diseases, and age-related macular degeneration (AMD) and diabetic retinopathy (DR) in elderly people, has been established. Disruption of the blood barrier function of the brain and retina is one of the most important underlying mechanisms associated with HHcy-induced neurodegenerative and retinal disorders. Impairment of the barrier function triggers inflammatory events that worsen disease pathology. Studies have shown that AD patients also suffer from visual impairments. As an extension of the central nervous system, the retina has been suggested as a prominent site of AD pathology. This review highlights inflammation as a possible underlying mechanism of HHcy-induced barrier dysfunction and neurovascular injury in aging diseases accompanied by HHcy, focusing on AD.

scholarly journals Biologically-Derived Nanomaterials for Targeted Therapeutic Delivery to the Brain

2018 ◽  
Vol 101 (3) ◽  
pp. 273-292
Author(s):  
Stephanie M. Curley ◽  
Nathaniel C. Cady
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Region Of Interest ◽  
Diagnosis And Treatment ◽  
Brain Diseases ◽  
Therapeutic Delivery ◽  
The Central Nervous System ◽  
Viral Nanoparticles ◽  
The Brain

Delivery of imaging agents and pharmaceutical payloads to the central nervous system (CNS) is essential for efficient diagnosis and treatment of brain diseases. However, therapeutic delivery is often restricted by the blood-brain barrier (BBB), which prevents transport of clinical compounds to their region of interest. This review discusses the methods that have been used to avoid or overcome this barrier, presenting the use of biologically-derived nanomaterial systems as an efficient strategy for the diagnosis and treatment of CNS diseases. Biological nanomaterials have many advantages over synthetic systems, including being biodegradable, biocompatible, easily surface functionalised for conjugation of targeting moieties, and are often able to self-assemble. These abilities are discussed in relation to various systems, including liposomes, dendrimers, and viral nanoparticles.

scholarly journals Protrudin functions as a scaffold in the endoplasmic reticulum to support axon regeneration in the adult central nervous system

2020 ◽  
Author(s):  
Veselina Petrova ◽  
Craig S. Pearson ◽  
James R. Tribble ◽  
Andrea G. Solano ◽  
Evan Reid ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Cortical Neurons ◽  
Binding Properties ◽  
Adult Central Nervous System ◽  
Low Levels ◽  
Cellular Components

SummaryAdult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.

Comparative aspects of brain barrier systems for nonelectrolytes

1978 ◽  
Vol 234 (1) ◽  
pp. R52-R60
Author(s):  
H. F. Cserr ◽  
J. D. Fenstermacher ◽  
D. P. Rall
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Barrier Function ◽  
Vertebrate Species ◽  
Detectable Change ◽  
Lemon Shark ◽  
Nurse Shark ◽  
Atlantic Stingray ◽  
The Central Nervous System ◽  
Brain Barriers

Blood-brain and blood-CSF barriers to inulin were compared in 11 vertebrate species. Twenty hours after systemic administration, [14C]inulin penetrated into the central nervous system to an equivalent extent in mudpuppy, salamander (adult and larval), red sculpin, big skate, little skate, southern stingray, and Atlantic stingray with values for RB (dpm/g brain divided by dpm/ml plasma) in the range 0.01- 0.04 and for RCSF (dpm/ml CSF divided by dpm/ml plasma) from 0.02 to 0.04. These values are similar to those reported for mammals. For dogfish, nurse shark, and lemon shark, RB ranged from 0.04 to 0.09 and RCSF from 0.08 to 0.29 and for hagfish RB=0.12, indicating that barrier systems to inulin are poorly developed in sharks and possibly absent in hagfish. Analyses of radiolabeled urea and sucrose penetration into brain and CSF revealed further differences in shark barrier function. Brain barriers to insulin in dogfish and little skate developed with age; in nurse shark there was no detectable change in the inulin ratios over the weight range, 0.2-110 kg.

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