scholarly journals Prion propagation in mice lacking central nervous system NF-κB signalling

2008 ◽  
Vol 89 (6) ◽  
pp. 1545-1550 ◽  
Author(s):  
C. Julius ◽  
M. Heikenwalder ◽  
P. Schwarz ◽  
A. Marcel ◽  
M. Karin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Published Data ◽  
Histopathological Changes ◽  
Prion Infection ◽  
Prion Propagation ◽  
Proliferation Regulation ◽  
The Impact ◽  
The Brain

Prions induce highly typical histopathological changes including cell death, spongiosis and activation of glia, yet the molecular pathways leading to neurodegeneration remain elusive. Following prion infection, enhanced nuclear factor-κB (NF-κB) activity in the brain parallels the first pathological changes. The NF-κB pathway is essential for proliferation, regulation of apoptosis and immune responses involving induction of inflammation. The IκB kinase (IKK) signalosome is crucial for NF-κB signalling, consisting of the catalytic IKKα/IKKβ subunits and the regulatory IKKγ subunit. This study investigated the impact of NF-κB signalling on prion disease in mouse models with a central nervous system (CNS)-restricted elimination of IKKβ or IKKγ in nearly all neuroectodermal cells, including neurons, astrocytes and oligodendrocytes, and in mice containing a non-phosphorylatable IKKα subunit (IKKα AA/AA). In contrast to previously published data, the observed results showed no evidence supporting the hypothesis that impaired NF-κB signalling in the CNS impacts on prion pathogenesis.

scholarly journals Neuropathogenesis caused by Trypanosoma brucei, still an enigma to be unveiled

2021 ◽  
Vol 8 (4) ◽  
pp. 73-76
Author(s):  
Katherine Figarella
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Trypanosoma Brucei ◽  
Late Stage ◽  
Early Stage ◽  
Tropical Diseases ◽  
The Central Nervous System ◽  
The Impact ◽  
The Brain

Trypanosoma brucei is one of the protozoa parasites that can enter the brain and cause injury associated with toxic effects of parasite-derived molecules or with immune responses against infection. Other protozoa parasites with brain tropism include Toxoplasma, Plasmodium, Amoeba, and, eventually, other Trypano-somatids such as T. cruzi and Leishmania. Together, these parasites affect billions of people worldwide and are responsible for more than 500.000 deaths annually. Factors determining brain tropism, mechanisms of in-vasion as well as processes ongoing inside the brain are not well understood. But, they depend on the par-asite involved. The pathogenesis caused by T. brucei initiates locally in the area of parasite inoculation, soon trypanosomes rich the blood, and the disease enters in the so-called early stage. The pathomecha-nisms in this phase have been described, even mole-cules used to combat the disease are effective during this period. Later, the disease evolves towards a late-stage, characterized by the presence of parasites in the central nervous system (CNS), the so-called meningo-encephalitic stage. This phase of the disease has not been sufficiently examined and remains a matter of investigation. Here, I stress the importance of delve into the study of the neuropathogenesis caused by T. brucei, which will enable the identification of path-ways that may be targeted to overcome parasites that reached the CNS. Finally, I highlight the impact that the application of tools developed in the last years in the field of neuroscience will have on the study of neglect-ed tropical diseases.

COVID-19, the Brain, and the Future: Is Infection by the Novel Coronavirus a Harbinger of Neurodegeneration?

2021 ◽  
Vol 21 ◽  
Author(s):  
Adejoke Onaolapo ◽  
Olakunle Onaolapo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Severe Acute Respiratory Syndrome ◽  
Neurodegenerative Diseases ◽  
Central Nervous System Involvement ◽  
The Novel ◽  
Novel Coronavirus ◽  
The Impact ◽  
The Brain

: The possible impact of viral infections on the development or pathogenesis of neurodegenerative disorders remains largely unknown. However, there have been reports associating the influenza virus pandemic and long-term infection with the Japanese encephalitis virus with the development of post-encephalitic Parkinsonism or von Economo encephalitis. In the last one year plus, there has been a worldwide pandemic arising from infection with the novel coronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 which causes a severe acute respiratory syndrome that has become associated with central nervous system symptoms or complications. Its possible central nervous system involvement is in line with emerging scientific evidence which shows that the human respiratory coronaviruses can enter the brain, infect neural cells, persist in the brain, and cause activation of myelin-reactive T cells. Currently, there is a dearth of scientific information on the acute or possible long-term impact of infection with SARS-CoV-2 on the development of dementias and/or neurodegenerative diseases. This is not unrelated to the fact that the virus is ‘new’, and its effects on humans are still being studied. This narrative review examines extant literature for the impact of corona virus infections on the brain; as it considers the possibility that coronavirus disease 2019 (COVID-19) could increase the risk for the development of neurodegenerative diseases or hasten their progression.

scholarly journals Sepsis-induced alterations in sleep of rats

2011 ◽  
Vol 301 (5) ◽  
pp. R1467-R1478 ◽  
Author(s):  
Francesca Baracchi ◽  
Ashley M. Ingiosi ◽  
Richard M. Raymond ◽  
Mark R. Opp
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Stem ◽  
Brain Temperature ◽  
Sleep Stage ◽  
Cecal Ligation ◽  
Clinical Problem ◽  
Sepsis Induction ◽  
The Impact ◽  
The Brain

Sepsis is a systemic immune response to infection that may result in multiple organ failure and death. Polymicrobial infections remain a serious clinical problem, and in the hospital, sepsis is the number-one noncardiac killer. Although the central nervous system may be one of the first systems affected, relatively little effort has been made to determine the impact of sepsis on the brain. In this study, we used the cecal ligation and puncture (CLP) model to determine the extent to which sepsis alters sleep, the EEG, and brain temperature (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye movement sleep (NREMS) during the dark period, but not during the light period. Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h following CLP surgery, after which REMS increases during dark periods for at least three nights. The EEG is dramatically altered shortly after sepsis induction, as evidenced by reductions in slow-frequency components. Furthermore, sleep is fragmented, indicating that the quality of sleep is diminished. Effects on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the duration of our recording period. Immunohistochemical assays focused on brain stem mechanisms responsible for alterations in REMS, as little information is available concerning infection-induced suppression of this sleep stage. Our immunohistochemical data suggest that REMS suppression after sepsis onset may be mediated, in part, by the brain stem GABAergic system. This study demonstrates for the first time that sleep and EEG patterns are altered during CLP-induced sepsis. These data suggest that the EEG may serve as a biomarker for sepsis onset. These data also contribute to our knowledge of potential mechanisms, whereby infections alter sleep and other central nervous system functions.

scholarly journals Methamphetamine Enhances Cryptococcus neoformans Pulmonary Infection and Dissemination to the Brain

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Dhavan Patel ◽  
Gunjan M. Desai ◽  
Susana Frases ◽  
Radames J. B. Cordero ◽  
Carlos M. DeLeon-Rodriguez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Respiratory Tract ◽  
Cryptococcus Neoformans ◽  
Biofilm Formation ◽  
Pulmonary Infection ◽  
Capsular Polysaccharide ◽  
Content Type ◽  
The Impact ◽  
The Brain

ABSTRACTMethamphetamine (METH) is a major addictive drug of abuse in the United States and worldwide, and its use is linked to HIV acquisition. The encapsulated fungusCryptococcus neoformansis the most common cause of fungal meningitis in patients with AIDS. In addition to functioning as a central nervous system stimulant, METH has diverse effects on host immunity. Using a systemic mouse model of infection andin vitroassays in order to critically assess the impact of METH onC. neoformanspathogenesis, we demonstrate that METH stimulates fungal adhesion, glucuronoxylomannan (GXM) release, and biofilm formation in the lungs. Interestingly, structural analysis of the capsular polysaccharide of METH-exposed cryptococci revealed that METH alters the carbohydrate composition of this virulence factor, an event of adaptation to external stimuli that can be advantageous to the fungus during pathogenesis. Additionally, we show that METH promotesC. neoformansdissemination from the respiratory tract into the brain parenchyma. Our findings provide novel evidence of the impact of METH abuse on host homeostasis and increased permissiveness to opportunistic microorganisms.IMPORTANCEMethamphetamine (METH) is a major health threat to our society, as it adversely changes people’s behavior, as well as increases the risk for the acquisition of diverse infectious diseases, particularly those that enter through the respiratory tract or skin. This report investigates the effects of METH use on pulmonary infection by the AIDS-related fungusCryptococcus neoformans. This drug of abuse stimulates colonization and biofilm formation in the lungs, followed by dissemination of the fungus to the central nervous system. Notably,C. neoformansmodifies its capsular polysaccharide after METH exposure, highlighting the fungus’s ability to adapt to environmental stimuli, a possible explanation for its pathogenesis. The findings may translate into new knowledge and development of therapeutic and public health strategies to deal with the devastating complications of METH abuse.

scholarly journals Central Nervous System Manifestations in Diabetes Mellitus - A Review

2017 ◽  
Vol 18 (2) ◽  
pp. 109-112
Author(s):  
Goutam Kumar Acherjya ◽  
Md Moslem Uddin ◽  
MA Jalil Chowdhury ◽  
AV Srinivasan
Keyword(s):  
Diabetes Mellitus ◽  
Central Nervous System ◽  
Nervous System ◽  
Stroke Risk ◽  
Diabetes Research ◽  
Seizure Disorders ◽  
Oral Agents ◽  
Hyperosmolar Coma ◽  
The Impact ◽  
The Brain

The impact of diabetes mellitus on the CNS (Central Nervous System) has gained attention only recently. Peripheral neuropathy has been the primary neuroscience focus of diabetes research. Contrary to some early impressions, however, the CNS is not spared by diabetes. Chronically, diabetes mellitus affects the CNS in several ways. Diabetes increases stroke risk and damage, overtreatment with insulin or oral agents can permanently damage the brain, and diabetes may increase the prevalence of seizure disorders. Diabetes changes brain transport, blood flow and metabolism, and may produce a chronic encephalopathy. Acutely, glycemic extremes cause coma, seizures, focal neurolclgical deficits, and impaired consciousness. The pathophysiological basis for these marked CNS abnormalities seen in hypoglycemia, hyperosmolar coma, and ketoacidosis are largely unknown.Methods: This review was based on a search of Pubmed, the NCBI Database of systemic Reviews, and citation lists of relevant publications. Subject heading and key words used central nervous system, diabetes mellitus, stroke, encephalopathy and hypoglycaemia. Only articles in English were included.J MEDICINE July 2017; 18 (2) : 109-112

scholarly journals Neuroinflammation, Microglia, and Cell-Association during Prion Disease

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 65 ◽  
Author(s):  
James Carroll ◽  
Bruce Chesebro
Keyword(s):  
Central Nervous System ◽  
Prion Disease ◽  
Host Defense ◽  
Prion Diseases ◽  
Infectious Agent ◽  
Prion Infection ◽  
Cell Association ◽  
Prion Propagation ◽  
The Central Nervous System ◽  
The Brain

Prion disorders are transmissible diseases caused by a proteinaceous infectious agent that can infect the lymphatic and nervous systems. The clinical features of prion diseases can vary, but common hallmarks in the central nervous system (CNS) are deposition of abnormally folded protease-resistant prion protein (PrPres or PrPSc), astrogliosis, microgliosis, and neurodegeneration. Numerous proinflammatory effectors expressed by astrocytes and microglia are increased in the brain during prion infection, with many of them potentially damaging to neurons when chronically upregulated. Microglia are important first responders to foreign agents and damaged cells in the CNS, but these immune-like cells also serve many essential functions in the healthy CNS. Our current understanding is that microglia are beneficial during prion infection and critical to host defense against prion disease. Studies indicate that reduction of the microglial population accelerates disease and increases PrPSc burden in the CNS. Thus, microglia are unlikely to be a foci of prion propagation in the brain. In contrast, neurons and astrocytes are known to be involved in prion replication and spread. Moreover, certain astrocytes, such as A1 reactive astrocytes, have proven neurotoxic in other neurodegenerative diseases, and thus might also influence the progression of prion-associated neurodegeneration.

scholarly journals Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Theodore S. Johnson ◽  
David H. Munn ◽  
Bernard L. Maria
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Infiltrating Lymphocytes ◽  
Tolerance Mechanism ◽  
Antigen Presenting ◽  
Open Question ◽  
Infiltrating Lymphocytes ◽  
The Impact ◽  
The Brain

Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

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