scholarly journals Unraveling of Central Nervous System Disease Mechanisms Using CRISPR Genome Manipulation

2018 ◽  
Vol 10 ◽  
pp. 117957351878746 ◽  
Author(s):  
Aino Vesikansa
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Complex Structure ◽  
Regulation Of Gene Expression ◽  
Central Nervous System Disease ◽  
Brain Diseases ◽  
Biological Research ◽  
Cns Diseases ◽  
The Brain

The complex structure and highly variable gene expression profile of the brain makes it among the most challenging fields to study in both basic and translational biological research. Most of the brain diseases are multifactorial and despite the rapidly increasing genomic data, molecular pathways and causal links between genes and central nervous system (CNS) diseases are largely unknown. The advent of an easy and flexible CRISPR-Cas genome editing technology has rapidly revolutionized the field of functional genomics and opened unprecedented possibilities to dissect the mechanisms of CNS disease. CRISPR-Cas allows a plenitude of applications for both gene-focused and genome-wide approaches, ranging from original “gene scissors” making permanent modifications in the genome to the regulation of gene expression and epigenetics. CRISPR technology provides a unique opportunity to establish new cellular and animal models of CNS diseases and holds potential for breakthroughs in the CNS research and drug development.

Current Overview of Inorganic Nanoparticles for the Treatment of Central Nervous System (CNS) Diseases

2020 ◽  
Vol 5 (2) ◽  
pp. 92-110
Author(s):  
Francesca Persano ◽  
Stefano Leporatti
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transport Processes ◽  
Inorganic Nanoparticles ◽  
Brain Diseases ◽  
Shell Nanoparticles ◽  
Cns Disorders ◽  
Cns Diseases ◽  
Design And Synthesis ◽  
The Brain

: Although the integrity of the Blood-brain Barrier (BBB) is often compromised in several Central nervous system (CNS) disorders, the release of therapeutic or diagnostic agents in the brain remains challenging. Indeed, most of the currently established diagnostic and therapeutic protocols result ineffective in treating and detecting CNS diseases. In this context, it is essential to develop novel strategies that allow a targeted release of the therapeutic agents to the brain, overcoming the BBB. The technological advances of the last decade have led to the development of new techniques for nanoscale treatment and diagnosis of brain diseases. : Several nano-formulations have been recently proposed and successfully tested in preclinical models for their capacity to cross the BBB, in particular when chemically modified with the intent to exploit specific transport processes that normally occur at the interface between blood and endothelium of the cerebral vasculature. : In this review, the tunable physico-chemical characteristics of inorganic nanoparticles will be reviewed, and how this aspect can offer the possibility to improve current therapeutic strategies. The local and systemic toxicity of these nanomaterials will be also analyzed. Furthermore, we will provide an update on recent key advancements in the design and synthesis of novel inorganic core-lipid shell nanoparticles for the treatment of CNS disorders, and how these vectors may overcome challenges faced by current inorganic nanomaterials.

scholarly journals Exosomes as cell-derivative carriers in the diagnosis and treatment of central nervous system diseases

2021 ◽  
Author(s):  
Gayatri Gopal Shetgaonkar ◽  
Shirleen Miriam Marques ◽  
Cleona E. M. DCruz ◽  
R. J. A. Vibhavari ◽  
Lalit Kumar ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Parenchyma ◽  
Brain Diseases ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Treatment And Diagnosis ◽  
The Brain

AbstractExosomes are extracellular vesicles with the diameter ranging from 50 to 100 nm and are found in different body fluids such as blood, cerebrospinal fluid (CSF), urine and saliva. Like in case of various diseases, based on the parent cells, the content of exosomes (protein, mRNA, miRNA, DNA, lipids and metabolites) varies and thus can be utilized as potential biomarker for diagnosis and prognosis of the brain diseases. Furthermore, utilizing the natural potential exosomes to cross the blood–brain barrier and by specifically decorating it with the ligand as per the desired brain sites therapeutics can be delivered to brain parenchyma. This review article conveys the importance of exosomes and their use in the treatment and diagnosis of brain/central nervous system diseases. Graphical abstract

scholarly journals Immune Response-Mediated Protection of Adult but Not Neonatal Mice from Neuron-Restricted Measles Virus Infection and Central Nervous System Disease

1999 ◽  
Vol 73 (3) ◽  
pp. 1795-1801 ◽  
Author(s):  
Diane M. P. Lawrence ◽  
Melinda M. Vaughn ◽  
Alec R. Belman ◽  
Joan S. Cole ◽  
Glenn F. Rall
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Neurological Disease ◽  
Measles Virus ◽  
Central Nervous System Disease ◽  
Nervous System Disease ◽  
Antiviral Immune Response ◽  
System Disease ◽  
The Brain

ABSTRACT In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46+ mice were back-crossed to T- and B-cell-deficient RAG-2 knockout mice. The lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46+RAG-2− mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection.

Electrophysiology of the central and peripheral nervous systems

2020 ◽  
pp. 5785-5802
Author(s):  
Christian Krarup
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Nerve Conduction Studies ◽  
Brain Diseases ◽  
The Core ◽  
Electrophysiological Studies ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

This chapter looks at electrophysiological studies of the central nervous system and peripheral nervous system—the core investigations in clinical neurophysiology. These include electroencephalography, which is of value to diagnose epilepsy caused by focal or diffuse brain diseases, electromyography and nerve conduction studies, which are of value to diagnose diseases in nerves and muscles, and evoked potentials, which are of value to diagnose diseases of white matter in the brain and spinal cord.

scholarly journals Differential Regulation of Interferon Regulatory Factor (IRF)-7 and IRF-9 Gene Expression in the Central Nervous System during Viral Infection

2005 ◽  
Vol 79 (12) ◽  
pp. 7514-7527 ◽  
Author(s):  
Shalina S. Ousman ◽  
Jianping Wang ◽  
Iain L. Campbell
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Viral Infection ◽  
Mononuclear Cells ◽  
Lymphocytic Choriomeningitis ◽  
The Central Nervous System ◽  
Ifn Γ ◽  
The Brain ◽  
Lcmv Infection

ABSTRACT Interferon regulatory factors (IRFs) are a family of transcription factors involved in the regulation of the interferons (IFNs) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. Therefore, we examined the regulation of IRF gene expression in the brain during viral infection. Several IRF genes (IRF-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. Following intracranial infection with lymphocytic choriomeningitis virus (LCMV), expression of the IRF-7 and IRF-9 genes increased significantly by day 2. IRF-7 and IRF-9 gene expression in the brain was widespread at sites of LCMV infection, with the highest levels in infiltrating mononuclear cells, microglia/macrophages, and neurons. IRF-7 and IRF-9 gene expression was increased in LCMV-infected brain from IFN-γ knockout (KO) but not IFN-α/βR KO animals. In the brain, spleen, and liver or cultured glial and spleen cells, IRF-7 but not IRF-9 gene expression increased with delayed kinetics in the absence of STAT1 but not STAT2 following LCMV infection or IFN-α treatment, respectively. The stimulation of IRF-7 gene expression by IFN-α in glial cell culture was prevented by cycloheximide. Thus, (i) many of the IRF genes were expressed constitutively in the mouse brain; (ii) the IRF-7 and IRF-9 genes were upregulated during viral infection, a process dependent on IFN-α/β but not IFN-γ; and (iii) IRF-7 but not IRF-9 gene expression can be stimulated in a STAT1-independent but STAT2-dependent fashion via unidentified indirect pathways coupled to the activation of the IFN-α/β receptor.

scholarly journals Gut microbiota regulate astrocytic functions in the brain: possible therapeutic consequences

2021 ◽  
Vol 19 ◽  
Author(s):  
Ya-Fei Zhao ◽  
Da-Neng Wei ◽  
Yong Tang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gut Microbiota ◽  
Clinical Studies ◽  
Brain Diseases ◽  
Psychiatric Diseases ◽  
Therapeutic Consequences ◽  
The Central Nervous System ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Astrocytes are essential for maintaining the homeostasis of the central nervous system (CNS). Astrocytic dysfunction has been implicated in the progression of several neurodegenerative and psychiatric diseases; however, a multitude of factors and signals influencing astrocytic activity have not been entirely elucidated. Astrocytes respond to local signals from the brain, but are also indirectly modulated by gut microbiota. Previous studies revealed that most of the CNS diseases triggered by astrocytic dysfunction are closely associated with the dysbiosis of gut microbiome. Emerging data from preclinical and clinical studies suggest that maturation and functioning of astrocytes rely on gut microbiota, which plays a pivotal role in the decrease of astrocytic activation and may alleviate symptoms of brain diseases. Herein, we discuss the most recent advances concerning the complex connections between astrocytes and gut microbiota, which are involved in the immune, neurotransmission and neuroendocrine pathways. Deciphering these pathways will facilitate a better understanding of how perturbed gut microbiota contributes to the dysfunction of astrocytes and open therapeutic opportunities for the treatment of brain diseases.

scholarly journals Phototherapeutic hardware complex for rehabilitation, prevention and treatment of diseases of the human central nervous system

2018 ◽  
Keyword(s):  
United States ◽  
Central Nervous System ◽  
Nervous System ◽  
The United States ◽  
Brain Diseases ◽  
Human Central Nervous System ◽  
Low Intensity ◽  
Hardware Complex ◽  
Post Traumatic ◽  
The Brain

Introduction. The significant prevalence of vascular diseases of the brain, the complexity of dysfunc- tion, put the problems of their treatment, rehabilitation and prevention into the focus of attention of modern neurology. A stroke occurs in the United States every 45 seconds. Approximately 750,000 people a year suffer from a stroke in the United States. According to statistics from the Ministry of Health of Ukraine, more than 110,000 primary strokes are recorded annually in the country. No less serious disease of the human central nervous system is Alzheimer’s disease. Each year, more than 500,000 Americans die from this disease, making it the third leading cause of death in the United States. Traffic accidents, local military conflicts, some sports form a very numerous specific group of patients with craniocerebral injuries. Aim — to develop a phototherapeutic hardware complex for the prevention, treatment and rehabilitation of vascular, inflammatory, degenerative, post-traumatic and other brain diseases that are difficult amenable to medical treatment including pharmacoresistant indomitable pain syndromes. Materials and methods. The low-intensity electromagnetic radiation of the optical range of the spectrum and the magnetic field of a permanent magnet are physical factors that are used in phototherapeutic complex devices. Results. A phototherapy apparatus complex has been developed for the prevention, treatment and reha- bilitation of vascular, inflammatory, degenerative, post-traumatic and other brain diseases that are difficult to treat with drugs. The phototherapeutic hardware complex includes three devices: the modified photon-mag- netic apparatus Korobov-Posokhov “Barva-CNS/FM”, the photon-magnetic matrices A.Korobov - V.Korobov “Barva-Laryngologist/FM” and flexible photon-magnetic matrices A.Korobov - V.Korobov “Barva-Flex/24FM”. Conclusions. The presented clinical observations obtained using the developed phototherapeutic hard-ware complex for the treatment and prevention of diseases of the brain indicate high efficacy and safety of long-term low-intensity phototherapy in patients with dyscirculatory encephalopathy, with suffered ischemic and hemorrhagic strokes, with hypertensive disease.

scholarly journals Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Takashi Mori ◽  
Takao Asano ◽  
Terrence Town
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Central Nervous System ◽  
Nervous System ◽  
Calcium Binding ◽  
Central Nervous System Disease ◽  
Adult Brain ◽  
Brain Inflammation ◽  
Brain Diseases ◽  
System Disease

S100B is an EF-hand calcium-binding protein that exerts both intracellular and extracellular effects on a variety of cellular processes. The protein is predominantly expressed in the central nervous system by astrocytes, both physiologically and during the course of neurological disease. In the healthy adult brain and during development, constitutive S100B expression acts as a trophic factor to drive neurite extension and to referee neuroplasticity. Yet, when induced during central nervous system disease, the protein can take on maladaptive roles and thereby exacerbate brain pathology. Based on genetic and pharmacological lines of evidence, we consider such deleterious roles of S100B in two common brain pathologies: ischemic stroke and Alzheimer's disease (AD). In rodent models of ischemic brain damage, S100B is induced early on during the subacute phase, where it exacerbates gliosis and delayed infarct expansion and thereby worsens functional recovery. In mouse models of AD, S100B drives brain inflammation and gliosis that accelerate cerebral amyloidosis. Pharmacological inhibition of S100B synthesis mitigates hallmark pathologies of both brain diseases, opening the door for translational approaches to treat these devastating neurological disorders.

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