scholarly journals Mechanisms of brain protection against autoimmune inflammation

2021 ◽  
Vol 13 (1S) ◽  
pp. 4-9
Author(s):  
A. I. Volkov ◽  
M. V. Melnikov ◽  
A. N. Boyko
Keyword(s):  
Immune System ◽  
Adaptive Immune Response ◽  
Perivascular Spaces ◽  
Regional Lymph Nodes ◽  
Autoimmune Inflammation ◽  
Self Tolerance ◽  
Choroid Plexuses ◽  
The Central Nervous System ◽  
Antigen Presenting ◽  
The Brain

A significant number of unique antigens expressed in the brain can activate an adaptive immune response, increasing the risk of autoimmune inflammation in the central nervous system (CNS). As a result, a complex protection system exists in the CNS to prevent autoimmune reactions. In addition to the blood-brain- and blood-cerebrospinal fluid-barriers, we discuss complex systems of antigen drainage and circulation of antigen-presenting cells in the CNS. Moreover, the interaction of the CNS with the peripheral immune system typically occurs in specific areas (choroid plexuses, perivascular spaces, and brain meninges), and resident cells of the innate immune system (macrophages, microglia, astrocytes) have limited opportunities for antigen presentation and do not migrate to regional lymph nodes. There are signs of activation of adaptive immunity against CNS antigens in normal conditions, which, however, do not lead to autoimmune diseases. The review covers the mechanisms of maintaining natural immune self-tolerance in the CNS and their failure in autoimmune CNS pathology.

Thiamine transport in the central nervous system

1976 ◽  
Vol 230 (4) ◽  
pp. 1101-1107 ◽  
Author(s):  
R Spector
Keyword(s):  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Simple Diffusion ◽  
Thiamine Transport ◽  
Choroid Plexuses ◽  
The Central Nervous System ◽  
The Brain ◽  
Thiamine Phosphates

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

scholarly journals Immune System in the Brain: A Modulatory Role on Dendritic Spine Morphophysiology?

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Oscar Kurt Bitzer-Quintero ◽  
Ignacio González-Burgos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Dendritic Spines ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
Brain Parenchyma ◽  
Immune Mediators ◽  
The Central Nervous System ◽  
The Brain

The central nervous system is closely linked to the immune system at several levels. The brain parenchyma is separated from the periphery by the blood brain barrier, which under normal conditions prevents the entry of mediators such as activated leukocytes, antibodies, complement factors, and cytokines. The myeloid cell lineage plays a crucial role in the development of immune responses at the central level, and it comprises two main subtypes: (1) resident microglia, distributed throughout the brain parenchyma; (2) perivascular macrophages located in the brain capillaries of the basal lamina and the choroid plexus. In addition, astrocytes, oligodendrocytes, endothelial cells, and, to a lesser extent, neurons are implicated in the immune response in the central nervous system. By modulating synaptogenesis, microglia are most specifically involved in restoring neuronal connectivity following injury. These cells release immune mediators, such as cytokines, that modulate synaptic transmission and that alter the morphology of dendritic spines during the inflammatory process following injury. Thus, the expression and release of immune mediators in the brain parenchyma are closely linked to plastic morphophysiological changes in neuronal dendritic spines. Based on these observations, it has been proposed that these immune mediators are also implicated in learning and memory processes.

scholarly journals Standarization of a Protocol of Immunohistochemistry for the Detection of Brain Microglia in Wistar Rats

2017 ◽  
Vol 19 (3) ◽  
pp. 45
Author(s):  
Karol Ramírez Chan DDS, MSc, PhD ◽  
Jaime Jaime Fornaguera-Trías PhD
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Wistar Rats ◽  
Secondary Antibody ◽  
Research Activity ◽  
The Central Nervous System ◽  
Near Future ◽  
The Brain ◽  
Microglia Morphology

Objective: Standardize a protocol of immunohistochemistry that has been widely used in C57BL/6J mice to identify microglia of the central nervous system in Wistar rats.  Materials and Methods: This research activity was carried out in two parts. In the first part, a protocol of immunohistochemistry was implemented to identify microglia in the central nervous system of 6 Wistar rats. A primary antibody with reactivity to rat and a specific secondary antibody to the primary were used. Once the protocol was established in rats' brains, an immunological challenge was produced with the intraperitoneal application of lipopolysaccharide in 2 Wistar rats, in order to evidence the changes in microglia morphology.  Results and Discussion: We demonstrate that without making major modifications to the original protocol, it can also be used to identify microglia in adult Wistar rats. In the near future, this immunostaining protocol will be applied to elucidate the bidirectional interaction between the brain and the immune system, under homeostatic conditions and different physiological and pathological stimuli.

scholarly journals The Influence of Somatic Pathology on the Health Status of Children With Attention Deficit Disorder and Hyperreactivity

2020 ◽  
Vol 6 (5) ◽  
pp. 128-136
Author(s):  
A. Matkeeva ◽  
E. Kondratieva
Keyword(s):  
Immune System ◽  
Attention Deficit ◽  
Attention Deficit Disorder ◽  
Control Group ◽  
Bioelectrical Activity ◽  
High Morbidity ◽  
The Central Nervous System ◽  
Delayed Maturation ◽  
Somatic Diseases ◽  
The Brain

The article studies the mechanisms of various types of formation of somatic diseases that underwent perinatal lesions of the central nervous system. And also, the study included 30 children with attention deficit disorder with hyperreactivity in combination with various somatic diseases aged 6 to 8 years and a control group of 30 children (children’s health). The study concluded that the severity of disorders depends on the level of neuropsychic development. Children showed high morbidity, delayed maturation of bioelectrical activity of the brain, impaired autoregulation of cerebral circulation, tension and overstrain of autonomic regulation, imbalance of the immune system, reflecting immaturity of the central, autonomic nervous, immune system.

scholarly journals Multiple Sclerosis: LIFNano-CD4 for Trojan Horse Delivery of the Neuro-Protective Biologic “LIF” Into the Brain: Preclinical Proof of Concept

2021 ◽  
Vol 3 ◽  
Author(s):  
Raul de la Flor ◽  
Janette Robertson ◽  
Rostislav V. Shevchenko ◽  
Mo Alavijeh ◽  
Sean Bickerton ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Self Tolerance ◽  
Current Therapies ◽  
Cognate Antigen ◽  
The Central Nervous System ◽  
Therapeutic Properties ◽  
Nano Formulation ◽  
The Brain ◽  
Treg Phenotype ◽  
Stem Cell Growth Factor

Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest late twenties. There is no cure, and current therapies are immunosuppressive only. LIF is a vital stem cell growth factor active throughout life—and essential for health of the central nervous system (CNS), being tolerogenic, myelinogenic, and neuroprotective. Nano-formulation of LIF (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic properties, increasing potency 1,000-fold when targeted to CD4 (LIFNano-CD4). Moreover, circulating CD4+ lymphocytes are themselves regulated by LIF to express the Treg phenotype, known to release T cell-derived LIF upon engagement with cognate antigen, perpetuating antigen-specific self-tolerance. With the longer-term aim of treating inflammatory lesions of MS, we asked, does LIFNano-CD4 cross the blood–brain barrier (BBB)? We measure pK and pD using novel methodologies, demonstrate crossing of the BBB, show LIF-cargo-specific anti-inflammatory efficacy in the frontal cortex of the brain, and show safety of intravenous delivery of LIFNano-CD4 at doses known to provide efficacious concentrations of LIF cargo behind the BBB.

scholarly journals The role of NOD2/CARD15 gene of antigen-presenting system in functioning of various organs and systems

2019 ◽  
Vol 100 (6) ◽  
Author(s):  
Maria Arkadevna Kazumian ◽  
Aleksander Vasilevich Vasilenok ◽  
Elena Dmitrievna Teplyakova
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Adaptive Immune Response ◽  
Receptor Activation ◽  
The Body ◽  
Activation Mechanism ◽  
Graft Versus Host Reaction ◽  
Nucleotide Oligomerization ◽  
Card15 Gene ◽  
Antigen Presenting

The article presents the literature review devoted to NOD2/CARD15 gene. Genetic variability affects the susceptibility and development of certain human diseases such as autoimmune diseases and infections, affecting numerous cellular processes, and thus modulating the response to environmental and internal factors. The NOD2/CARD15 gene plays a major role in the development and course of various diseases such as Grohn's disease, Blau syndrome, as well as the risk of developing severe complications of the graft versus host reaction after allogeneic stem cell transplantation. NOD (Nucleotide Oligomerization Domain) is the domain of nucleotide oligomerization. NOD-like receptors play an important regulatory role in the response on infectious agents and at activation of the adaptive immune response. It is known that the mechanism of action of NOD-like receptors is based on the response to the pathogen of associated molecular patterns mainly of bacterial origin, which leads to the formation and activation of inflammasome. Recently, another NOD-like receptor activation mechanism has been revealed that provides innate virus recognition. The review presents Toll-like receptors, which are part of the innate immune system. Innate immunity is an inherited system of protection of the body against pathogenic and non-pathogenic microorganisms. The mechanisms of innate immunity develop very quickly. In newborns, the immune system is mainly dependent on components of the innate or antigen-independent immune system including phagocytes, natural killer cells, antigen-presenting cells, humoral inflammatory mediators and complement system.

Regulating Systems in Neuroimmunology

2021 ◽  
Author(s):  
William H. Walker II ◽  
A. Courtney DeVries
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Scientific Investigation ◽  
Neuroimmune System ◽  
Disease States ◽  
Behavioral Abnormalities ◽  
Optimal Health ◽  
The Central Nervous System ◽  
Active Research ◽  
The Brain

Neuroimmunology is the study of the interaction between the immune system and nervous system during development, homeostasis, and disease states. Descriptions of neuroinflammatory diseases dates back centuries. However, in depth scientific investigation in the field began in the late 19th century and continues into the 21st century. Contrary to prior dogma in the field of neuroimmunology, there is immense reciprocal crosstalk between the brain and the immune system throughout development, homeostasis, and disease states. Proper neuroimmune functioning is necessary for optimal health, as the neuroimmune system regulates vital processes including neuronal signaling, synapse pruning, and clearance of debris and pathogens within the central nervous system. Perturbations in optimal neuroimmune functioning can have detrimental consequences for the host and underlie a myriad of physical, cognitive, and behavioral abnormalities. As such, the field of neuroimmunology is still relatively young and dynamic and represents an area of active research and discovery.

scholarly journals Perivascular and Perineural Pathways Involved in Brain Delivery and Distribution of Drugs after Intranasal Administration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 598 ◽  
Author(s):  
Jeffrey J. Lochhead ◽  
Thomas P. Davis
Keyword(s):  
Current Evidence ◽  
Perivascular Spaces ◽  
Brain Delivery ◽  
Physiological Conditions ◽  
Routes Of Administration ◽  
Disease States ◽  
Efficient Delivery ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood–brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.

Networks and Teleology

1988 ◽  
Vol 14 ◽  
pp. 159-186
Author(s):  
Edwin Levy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Functional Network ◽  
The Central Nervous System ◽  
The Brain ◽  
New Hypothesis

In 1973 Niels Kaj Jerne announced an important new hypothesis about the immune system (‘IS’). That suggestion is based on several similarities between IS and the central nervous system. Jerne postulated that IS, like the nervous system, is a network.I am convinced that the description of the immune system as a functional network of lymphocytes and antibody molecules is essential to its understanding, and that the network as a whole functions in a way that is peculiar to and characteristic of the internal interactions of the elements of the immune system itself: it displays what I call eigen-behavior. (Jerne [1973), 59)This proposal has a number of implications, including some philosophical ones. Here I focus on the question whether the network hypothesis and subsequent developments shed any light on the use of teleological concepts in biology. In part one I present some of the background story of network ideas in immunology, including a reverse hypothesis to the effect that IS-Net could serve as a basis for modeling the brain. In part two I locate the teleological implications of IS-Net with respect to current mainstream discussions of teleology.

Sign in / Sign up

Export Citation Format

Share Document