scholarly journals Urease Expression by Cryptococcus neoformans Promotes Microvascular Sequestration, Thereby Enhancing Central Nervous System Invasion

2004 ◽  
Vol 164 (5) ◽  
pp. 1761-1771 ◽  
Author(s):  
Michal A. Olszewski ◽  
Mairi C. Noverr ◽  
Gwo-Hsiao Chen ◽  
Galen B. Toews ◽  
Gary M. Cox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Central Nervous System Invasion

scholarly journals Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Jennifer L. Tenor ◽  
Stefan H. Oehlers ◽  
Jialu L. Yang ◽  
David M. Tobin ◽  
John R. Perfect
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Central Nervous System Infection ◽  
Live Imaging ◽  
Infection Model ◽  
Content Type ◽  
Cryptococcal Infection ◽  
Zebrafish Larvae ◽  
Central Nervous System Invasion

ABSTRACTThe human fungal pathogenCryptococcus neoformansis capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions ofCryptococcuswith the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel ofCryptococcusmutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals thatC. neoformansis able to penetrate the zebrafish brain following intravenous infection. By studying aC. neoformansFNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformansplatform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents.IMPORTANCECryptococcus neoformansis an important opportunistic pathogen that is estimated to be responsible for more than 600,000 deaths worldwide annually. Existing mammalian models of cryptococcal pathogenesis are costly, and the analysis of important pathogenic processes such as meningitis is laborious and remains a challenge to visualize. Conversely, although invertebrate models of cryptococcal infection allow high-throughput assays, they fail to replicate the anatomical complexity found in vertebrates and, specifically, cryptococcal stages of disease. Here we have utilized larval zebrafish as a platform that overcomes many of these limitations. We demonstrate that the pathogenesis ofC. neoformansinfection in zebrafish involves factors identical to those in mammalian and invertebrate infections. We then utilize the live-imaging capacity of zebrafish larvae to follow the progression of cryptococcal infection in real time and establish a relevant model of the critical central nervous system infection phase of disease in a nonmammalian model.

scholarly journals Persistent cognitive impairment associated with cerebrospinal fluid anti-SARS-CoV-2 antibodies six months after mild COVID-19

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Max Borsche ◽  
Dirk Reichel ◽  
Anja Fellbrich ◽  
Anne S. Lixenfeld ◽  
Johann Rahmöller ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Cognitive Impairment ◽  
Female Patient ◽  
Acute Phase ◽  
Neuropsychological Testing ◽  
Important Challenge ◽  
Central Nervous System Invasion

AbstractNeurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cognitive impairment along with persistent cerebrospinal fluid anti-SARS-CoV-2 antibodies in a female patient with unremarkable standard examination 6 months after mild COVID-19, supporting the implementation of neuropsychological testing and specific cerebrospinal fluid investigation also in patients with a relatively mild acute disease phase.

scholarly journals Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

2011 ◽  
Vol 11 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Jim Kronstad ◽  
Sanjay Saikia ◽  
Erik David Nielson ◽  
Matthias Kretschmer ◽  
Wonhee Jung ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Central Carbon Metabolism ◽  
Yeast Cells ◽  
Phagocytic Cells ◽  
Content Type ◽  
The Central Nervous System ◽  
Mechanisms Of Adaptation ◽  
Complex Integration

ABSTRACTThe basidiomycete fungusCryptococcus neoformansinfects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors ofC. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.

Autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluids are useful for the diagnosis of central nervous system invasion caused by haematological malignancies

2019 ◽  
Vol 56 (2) ◽  
pp. 240-246 ◽  
Author(s):  
Takuya Shimura ◽  
Makoto Kurano ◽  
Yoshifumi Morita ◽  
Naoyuki Yoshikawa ◽  
Masako Nishikawa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Diagnostic Imaging ◽  
Haematological Malignancies ◽  
Serum Concentrations ◽  
Receptor Concentration ◽  
The Central Nervous System ◽  
Central Nervous System Invasion ◽  
Strong Ability

Background Invasion of the central nervous system by haematological malignancies is diagnosed by cytological analyses of cerebrospinal fluid or diagnostic imaging, while quantitative biomarkers for central nervous system invasion are not available and needed to be developed. Methods In this study, we measured the concentrations of autotaxin and soluble IL-2 receptor in cerebrospinal fluid and evaluated their usefulness as biomarkers for central nervous system invasion. Results We observed that both the autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluid were higher in subjects with central nervous system invasion than in those without, and the cerebrospinal fluid concentrations were independent from the serum concentrations of these biomarkers. ROC analyses revealed that the soluble IL-2 receptor concentration in cerebrospinal fluid was a strong discriminator of central nervous system invasion in subjects with haematological malignancies, while the autotaxin concentration in cerebrospinal fluid also had a strong ability to discriminate central nervous system invasion when the subjects were limited to those with lymphoma. The combined measurement of autotaxin and soluble IL-2 receptor in cerebrospinal fluid improved the sensitivity without notably reducing the specificity for central nervous system invasion in subjects with lymphoma when central nervous system invasion was diagnosed in cases where either value was beyond the respective cut-off value. Conclusion These results suggest the possible usefulness of soluble IL-2 receptor and autotaxin concentrations in cerebrospinal fluid for the diagnosis of central nervous system invasion.

Indications for, Contraindications to, and Interruption of Craniofacial Procedures

1997 ◽  
Vol 106 (11) ◽  
pp. 927-933 ◽  
Author(s):  
Claudio R. Cernea ◽  
Gilberto V. Teixeira ◽  
Eduardo A. S. Vellutini ◽  
Luiz R. Medina dos Santos ◽  
Mário G. Siqueira
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Skull Base ◽  
Malignant Tumors ◽  
Purulent Discharge ◽  
Benign Tumors ◽  
Histologic Diagnosis ◽  
Lateral Skull Base ◽  
Central Nervous System Invasion ◽  
Orbital Invasion

In spite of increasing experience with skull base surgery, some of the guidelines for indications for operations may vary according to the institution. One-hundred two patients underwent craniofacial oncologic resections at our institution from 1982 to 1995. A retrospective analysis of the indications for and contraindications to these procedures was undertaken. The main indications for malignant tumors were skin lesions with direct invasion of the anterior or lateral skull base (69%) and nasal-paranasal sinus tumors (21%). The main indications for benign tumors were glomus lesions (26%), menigiomas (22%), and fibro-osseous lesions of the anterior skull base (19%). The main contraindications were extensive invasion of the central nervous system, invasion of the cavernous sinus and/or internal carotid artery by aggressive malignancies, and bilateral orbital invasion in a nonblind patient. Also, 6 patients had their procedures interrupted during craniotomy for several reasons — extensive central nervous system invasion (2 cases), bilateral orbital invasion (1), lack of brain retraction (1), lack of histologic diagnosis during the operation (1), and purulent discharge at the frontal sinus (1). Craniofacial oncologic operations are extensive surgical procedures that have to be properly indicated in order to obtain low levels of morbidity and mortality. The selection of cases is of paramount importance. In some instances, it seems advisable even to interrupt these operations in the first phase.

Feline cryptococcosis: a retrospective evaluation

1997 ◽  
Vol 33 (2) ◽  
pp. 118-122 ◽  
Author(s):  
S Gerds-Grogan ◽  
B Dayrell-Hart
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Clinical Pathology ◽  
Fungal Disease ◽  
University Of Pennsylvania ◽  
Retrospective Evaluation ◽  
Cns Involvement ◽  
The University ◽  
Veterinary Hospital

Cryptococcus neoformans causes the most common form of feline systemic fungal disease. Nineteen cats with cryptococcosis were seen at the Veterinary Hospital of the University of Pennsylvania between April 1986 and May 1995. Compared to other studies, these 19 cases showed increased neurological and ophthalmological involvement. Males were affected more often than females. Season and environment appeared to influence time of onset or presentation to the hospital. Clinical pathology did not show typical changes. It is possible that the organism was present frequently in the urine but was mistaken for fat droplets. Treatment with ketoconazole was unrewarding in cases with central nervous system (CNS) involvement.

scholarly journals Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by experimental infection in BALB/c mice and correlation with exoenzyme activity

2006 ◽  
Vol 55 (2) ◽  
pp. 139-142 ◽  
Author(s):  
Eriques Gonçalves da Silva ◽  
Francisco de Assis Baroni ◽  
Flavio César Viani ◽  
Luciana da Silva Ruiz ◽  
Rinaldo Ferreira Gandra ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cryptococcus Neoformans ◽  
Experimental Infection ◽  
The Other ◽  
Death Rates ◽  
Before And After ◽  
The Central Nervous System ◽  
Neurological Infection

To evaluate the virulence profile of strains of Cryptococcus neoformans var. grubii, 62 strains of this yeast were inoculated into BALB/c mice. It was found that 69 % of the strains were significantly more lethal to the mice and were recovered from a higher percentage (60 %) of the organs compared with the other 31 % of the strains, which were recovered from 35 % of organs tested. Those strains that provoked higher death rates were also recovered from the central nervous system at a higher rate (84 %) than the less lethal strains (32 %). This finding led to an investigation of the factors that enhanced the capacity for neurological infection and death of the animals. The results of this study suggested that environmental strains present different degrees of virulence. The correlation of exoenzyme production before and after inoculation and between the groups of mice indicated that exoenzyme production had no influence on differences in virulence among the strains studied.

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