scholarly journals A murine model of Lyme disease demonstrates that Borrelia burgdorferi colonizes the dura mater and induces inflammation in the central nervous system

2021 ◽  
Vol 17 (2) ◽  
pp. e1009256
Author(s):  
Timothy Casselli ◽  
Ali Divan ◽  
Emilie E. Vomhof-DeKrey ◽  
Yvonne Tourand ◽  
Heidi L. Pecoraro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lyme Disease ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Dura Mater ◽  
Laboratory Mice ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Kinetics Of

Lyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Inbred laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in joints and heart, however similar studies are lacking in the CNS of these animals. A tractable animal model for investigating host-Borrelia interactions in the CNS is key to understanding the mechanisms of CNS pathogenesis. Therefore, we characterized the kinetics of B. burgdorferi colonization and associated immune responses in the CNS of mice during early and subacute infection. Using fluorescence-immunohistochemistry, intravital microscopy, bacterial culture, and quantitative PCR, we found B. burgdorferi routinely colonized the dura mater of C3H mice, with peak spirochete burden at day 7 post-infection. Dura mater colonization was observed for several Lyme disease agents including B. burgdorferi, B. garinii, and B. mayonii. RNA-sequencing and quantitative RT-PCR showed that B. burgdorferi infection was associated with increased expression of inflammatory cytokines and a robust interferon (IFN) response in the dura mater. Histopathologic changes including leukocytic infiltrates and vascular changes were also observed in the meninges of infected animals. In contrast to the meninges, we did not detect B. burgdorferi, infiltrating leukocytes, or large-scale changes in cytokine profiles in the cerebral cortex or hippocampus during infection; however, both brain regions demonstrated similar changes in expression of IFN-stimulated genes as observed in peripheral tissues and meninges. Taken together, B. burgdorferi is capable of colonizing the meninges in laboratory mice, and induces localized inflammation similar to peripheral tissues. A sterile IFN response in the absence of B. burgdorferi or inflammatory cytokines is unique to the brain parenchyma, and provides insight into the potential mechanisms of CNS pathology associated with this important pathogen.

scholarly journals A Murine Model of Lyme Disease Demonstrates That Borrelia burgdorferi Colonizes the Dura Mater and Induces Inflammation in the Central Nervous System

2020 ◽  
Author(s):  
Timothy Casselli ◽  
Ali Divan ◽  
Yvonne Tourand ◽  
Heidi L. Pecoraro ◽  
Catherine A. Brissette
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Dura Mater ◽  
Brain Parenchyma ◽  
The Central Nervous System ◽  
Effective Models

ABSTRACTLyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Inbred laboratory mice are effective models for characterizing B. burgdorferi infection kinetics and host immune responses in joints and heart tissues; however, similar studies are lacking in the CNS of these animals. Here we characterize the kinetics of B. burgdorferi colonization and associated immune responses in the CNS of infected C3H mice during early and subacute infection. B. burgdorferi colonized the dura mater following needle or tick challenge, and induced expression of inflammatory cytokines and a robust IFN response as well as histopathological changes. A sterile IFN response in the absence of B. burgdorferi or inflammatory cytokines was unique to the brain parenchyma, and could provide insights into the mechanism of inflammatory CNS pathology associated with this important pathogen.

scholarly journals Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes

2021 ◽  
Vol 22 (4) ◽  
pp. 1587
Author(s):  
Nuri Song ◽  
Da Yeon Jeong ◽  
Thai Hien Tu ◽  
Byong Seo Park ◽  
Hye Rim Yang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Nutrient Availability ◽  
Acid Oxidation ◽  
Cell Type ◽  
Metabolic Processes ◽  
Nutrient Metabolism ◽  
Peripheral Tissues ◽  
The Central Nervous System

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.

Cerebrospinal Fluid Cytology of Lyme Neuroborreliosis: A Report of 3 Cases with Literature Review

2015 ◽  
Vol 59 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Juan Xing ◽  
Lisa Radkay ◽  
Sara E. Monaco ◽  
Christine G. Roth ◽  
Liron Pantanowitz
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lyme Disease ◽  
B Cell ◽  
Plasma Cells ◽  
Lyme Neuroborreliosis ◽  
Chain Analysis ◽  
The Central Nervous System

Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma.

scholarly journals Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission

2001 ◽  
Vol 82 (10) ◽  
pp. 2319-2326 ◽  
Author(s):  
J. D. Foster ◽  
D. W. Parnham ◽  
N. Hunter ◽  
M. Bruce
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Infection ◽  
Oral Route ◽  
Similar Distribution ◽  
Peripheral Tissues ◽  
Oral Transmission ◽  
Wide Range ◽  
Direct Contrast ◽  
The Central Nervous System

This study has examined the distribution of PrPSc in sheep by immunocytochemistry of tissues recovered from terminally affected animals following their experimental infection by the oral route with BSE. Despite a wide range of incubation period lengths, affected sheep showed a similar distribution of high levels of PrPSc throughout the central nervous system. PrPSc was also found in the lymphoid system, including parts of the digestive tract, and some components of the peripheral nervous system. These abundant PrPSc deposits in sheep in regions outside the central nervous system are in direct contrast with cattle infected with BSE, which show barely detectable levels of PrPSc in peripheral tissues. A number of genetically susceptible, challenged animals appear to have survived.

scholarly journals Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy M. OʼShea ◽  
Alexander L. Wollenberg ◽  
Jae H. Kim ◽  
Yan Ao ◽  
Timothy J. Deming ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Foreign Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Peripheral Tissues ◽  
Molecular Delivery ◽  
Wound Responses ◽  
The Central Nervous System

AbstractBiomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.

Urea transport in the central nervous system

1962 ◽  
Vol 203 (4) ◽  
pp. 739-747 ◽  
Author(s):  
Charles R. Kleeman ◽  
Hugh Davson ◽  
Emanuel Levin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nervous Tissue ◽  
Urea Transport ◽  
Major Barrier ◽  
Rate Of Penetration ◽  
The Central Nervous System ◽  
Kinetics Of ◽  
The Brain ◽  
State Content

The kinetics of urea transport in the central nervous system have been studied in rabbits during sustained intravenous and intracisternal infusions of C12 and C14 urea. The steady state content of urea in the water phase of the white matter and cord was approximately equal to its content in plasma water. However, the water of whole brain and gray matter had levels of urea which exceeded those in plasma by 7 and 18%, respectively, whereas the urea in cerebrospinal fluid (CSF) was only 78% of the plasma level. Its rate of penetration into nervous tissue was approximately one-tenth as rapid as into muscle. The intravenous infusion of urea caused a significant decrease in water content of the brain and cord. It was estimated that urea infused into the subarachnoid space penetrated the central nervous system (CNS) tissues at four to five times the rate of transport from blood to CNS tissues. These studies suggest that intravenous infusions of urea lower CSF pressure by decreasing the volume of the brain and cord. The major barrier to urea penetration into nervous tissue is at the capillary level, and not the plasma membrane of the glial or neuronal cells.

scholarly journals n-3 PUFA and obesity: from peripheral tissues to the central nervous system

2018 ◽  
Vol 119 (11) ◽  
pp. 1312-1323 ◽  
Author(s):  
Aline Haas de Mello ◽  
Marcela Fornari Uberti ◽  
Bianca Xavier de Farias ◽  
Nathalia Alberti Ribas de Souza ◽  
Gislaine Tezza Rezin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cardiac Arrhythmias ◽  
The Body ◽  
Low Grade ◽  
Therapeutic Approaches ◽  
Peripheral Tissues ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Inflammatory Effect

AbstractThe current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).

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