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CNS Infection

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81. What Kaplan-Meier Survival Curves Don’t Tell Us About CNS Disease (Full text)

What Kaplan-Meier Survival Curves Don’t Tell Us About CNS Disease Central nervous system consequences of viral infections are rare, but when they do occur, they are often serious and clinically challenging to manage. Our awareness of the perils of neuroinvasion by viruses is growing: the recently appreciated impact of Ebola and Zika virus infections on CNS integrity, decreases in vaccination coverage for potentially neurotropic viruses such as measles, and increased neurovirulence of some (...) influenza strains collectively highlight the need for a better understanding of the viral-neural interaction. Defining these interactions and how they result in neuropathogenesis is paramount for the development of better clinical strategies, especially given the limited treatment options that are available due to the unique physiology of the brain that limits migration of blood-borne molecules into the CNS parenchyma. In this perspective, we discuss some unique aspects of neuronal viral infections

2017 Journal of Neuroimmunology PubMed

82. Feline Immunodeficiency Virus Neuropathogenesis: A Model for HIV-Induced CNS Inflammation and Neurodegeneration (Full text)

Feline Immunodeficiency Virus Neuropathogenesis: A Model for HIV-Induced CNS Inflammation and Neurodegeneration Feline Immunodeficiency virus (FIV), similar to its human analog human immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after infection and establishes a protected viral reservoir. The ensuing inflammation and damage give rise to varying degrees of cognitive decline collectively known as HIV-associated neurocognitive disorders (HAND). Because (...) of the similarities to HIV infection and disease, FIV has provided a useful model for both in vitro and in vivo studies of CNS infection, inflammation and pathology. This mini review summarizes insights gained from studies of early infection, immune cell trafficking, inflammation and the mechanisms of neuropathogenesis. Advances in our understanding of these processes have contributed to the development of therapeutic interventions designed to protect neurons and regulate inflammatory activity.

2017 Veterinary Sciences PubMed

83. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization- case study (Full text)

a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier (...) Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization- case study Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from

2017 Journal of neurovirology PubMed

84. Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells (Full text)

Investigation of ac-magnetic field stimulated nanoelectroporation of magneto-electric nano-drug-carrier inside CNS cells In this research, we demonstrate cell uptake of magneto-electric nanoparticles (MENPs) through nanoelectroporation (NEP) using alternating current (ac)-magnetic field stimulation. Uptake of MENPs was confirmed using focused-ion-beam assisted transmission electron microscopy (FIB-TEM) and validated by a numerical simulation model. The NEP was performed in microglial (MG) brain (...) cells, which are highly sensitive for neuro-viral infection and were selected as target for nano-neuro-therapeutics. When the ac-magnetic field optimized (60 Oe at 1 kHz), MENPs were taken up by MG cells without affecting cell health (viability > 92%). FIB-TEM analysis of porated MG cells confirmed the non-agglomerated distribution of MENPs inside the cell and no loss of their elemental and crystalline characteristics. The presented NEP method can be adopted as a part of future nanotherapeutics

2017 Scientific reports PubMed

85. Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen (Full text)

in significant amelioration of PLP178-191-induced EAE. Disease suppression was not observed in mice deficient in CD8 T-cells, IFN-γ or perforin. DTH responses and CNS infiltration were reduced in protected mice, and their CD4 T-cells had reduced capacity to induce tissue inflammation. Importantly, infection with LM-PLP ameliorated established disease. Our studies indicate that CD8 T-cells induced by endogenous presentation of PLP178-191 attenuate CNS autoimmunity in models of EAE, implicating the potential (...) Suppression of autoimmune demyelinating disease by preferential stimulation of CNS-specific CD8 T cells using Listeria-encoded neuroantigen CD8 T-cells predominate in CNS lesions of MS patients and display oligoclonal expansion. However, the role of myelin-specific CD8 T-cells in disease remains unclear, with studies showing protective and pathogenic roles in EAE. We demonstrated a disease-suppressive function for CNS-specific CD8 T-cells in a model where the antigen is exogenously administered

2017 Scientific reports PubMed

86. An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation (Full text)

An optimized method for enumerating CNS derived memory B cells during viral-induced inflammation CNS inflammation resulting from infection, injury, or neurodegeneration leads to accumulation of diverse B cell subsets. Although antibody secreting cells (ASC) within the inflamed CNS have been extensively examined, memory B cell (Bmem) characterization has been limited as they do not secrete antibody without stimulation. Moreover, unlike human Bmem, reliable surface markers for murine Bmem remain (...) in the presence of feeder cells for 2days.Flow cytometry markers CD38 and CD73 characterizing murine Bmem from lymphoid tissue showed more diverse expression patterns on corresponding CNS-derived B cell subsets. Using the optimized TLR7/8 stimulation protocol, we compared virus-specific IgG Bmem versus pre-existing ASC within the brain and spinal cord. Increasing Bmem frequencies during chronic infection mirrored kinetics of ASC. However, despite initially similar Bmem and ASC accumulation, Bmem prevailed

2017 Journal of neuroscience methods PubMed

87. Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment (Full text)

Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before (...) SCT.We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed.Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic

2017 Practical radiation oncology PubMed

88. A Neuroprimer: Principles of CNS Immunity (Full text)

A Neuroprimer: Principles of CNS Immunity Despite longstanding perceptions, robust innate and adaptive immune responses occur within the central nervous system (CNS) in response to infection and tissue damage. Although necessary to control infection, immune responses can lead to severe CNS pathology in the context of both viral infection and autoimmunity. Research into how the central nervous and immune systems communicate has accelerated over the past 20 years leading to a better understanding (...) of pathways controlling immune activation and neuroinflammation that have guided the approval of new disease-modifying therapies to treat CNS immunopathology, particularly the inflammatory demyelinating disease multiple sclerosis. This article provides an introduction into the basic principles underlying immune responses within the CNS that developed from experimental animal models of both neurotropic virus infection and autoimmune T cell-mediated CNS demyelination.Copyright © 2017 Elsevier Inc. All

2017 Seminars in pediatric neurology PubMed

89. Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis (Full text)

post-infection. The combination of the three methodologies indicates that changes in the CNS become apparent prior to the onset of established stage-2 disease. This could in part account for the difficulties associated with defining specific criteria to distinguish stage-1 and stage-2 infections and highlights the need for improved staging diagnostics.Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. (...) Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance

2017 Methods (San Diego, Calif.) PubMed

90. A SIV molecular clone that targets the CNS and induces neuroAIDS in rhesus macaques (Full text)

A SIV molecular clone that targets the CNS and induces neuroAIDS in rhesus macaques Despite effective control of plasma viremia with the use of combination antiretroviral therapies (cART), minor cognitive and motor disorders (MCMD) persist as a significant clinical problem in HIV-infected patients. Non-human primate models are therefore required to study mechanisms of disease progression in the central nervous system (CNS). We isolated a strain of simian immunodeficiency virus (SIV), SIVsm804E (...) . NeuroAIDS was also induced in macaques co-inoculated with CL757 and the parental AIDS-inducing, but non-neurovirulent SIVsmE543-3 (E543-3). Molecular analysis of macaques infected with CL757 revealed compartmentalization of virus populations between the CNS and the periphery. CL757 exclusively targeted the CNS whereas E543-3 was restricted to the periphery consistent with a role for viral determinants in the mechanisms of neuroinvasion. CL757 would be a useful model to investigate disease progression

2017 PLoS pathogens PubMed

91. HIV Cure Strategists: Ignore the CNS at Your Patients’ Peril (Full text)

HIV Cure Strategists: Ignore the CNS at Your Patients’ Peril 27898594 2018 09 28 2018 11 13 1473-5571 31 1 2017 01 02 AIDS (London, England) AIDS HIV cure strategists: ignore the central nervous system at your patients' peril. 167-168 Spector Stephen A SA aDepartment of Pediatrics, University of California San Diego, La Jolla bRady Children's Hospital San Diego, California cDepartment of Neuroscience and Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia (...) , Pennsylvania, United States. Rappaport Jay J eng P01 MH105303 MH NIMH NIH HHS United States R01 AI039004 AI NIAID NIH HHS United States R01 NS084912 NS NINDS NIH HHS United States R01 MH090910 MH NIMH NIH HHS United States R01 MH101010 MH NIMH NIH HHS United States R01 NS077874 NS NINDS NIH HHS United States Editorial Comment England AIDS 8710219 0269-9370 IM X AIDS. 2017 Jan 2;31(1):5-14 27898590 Central Nervous System HIV Infections Humans There are no conflict of interests. 2016 11 30 6 0 2016 11 30 6 0

2017 AIDS (London, England) PubMed

92. A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder (Full text)

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case (...) of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent

2017 Case reports in oncological medicine PubMed

93. The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders (Full text)

to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions. (...) The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson's disease, Alzheimer's disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical

2017 Frontiers in cellular neuroscience PubMed

94. CNS-targeted autoimmunity leads to increased influenza mortality in mice (Full text)

CNS-targeted autoimmunity leads to increased influenza mortality in mice The discovery that central nervous system (CNS)-targeted autoreactive T cells required a process of licensing in the lung revealed an unexpected relationship between these organs. The clinical and immunological significance of this finding is bidirectional in that it showed not only a mechanism by which T cells become pathogenic before entering the CNS, but also the potential for this process to influence lung immunity (...) as well. Epidemiological studies have shown that people with multiple sclerosis (MS) suffer from increased morbidity and mortality from infectious diseases, independent of immunosuppressive therapies. Respiratory infections account for a large percentage of deaths of people with MS. In this study, to investigate the mechanisms responsible for this enhanced susceptibility, we established a comorbid model system in which mice with experimental autoimmune encephalomyelitis (EAE) were administered

2017 The Journal of experimental medicine PubMed

95. Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS (Full text)

Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS Rabies virus induces drastic behaviour modifications in infected hosts. The mechanisms used to achieve these changes in the host are not known. The main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine (...) into the central nervous system of mice. These results provide a mechanistic explanation for the behavioural changes in hosts infected by rabies virus.

2017 Scientific reports PubMed

96. Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate (Full text)

that FTY interferes with integrin activation.In addition to NTZ, DMF and FTY but not other tested DMTs may also decrease T-cell-mediated immune surveillance of the CNS. Whether this mechanism may contribute to the onset of CNS opportunistic infections remains to be shown. (...) Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile.We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7

2017 Neurology® neuroimmunology & neuroinflammation PubMed

97. Mechanisms of CNS Viral Seeding by HIV+ CD14+ CD16+ Monocytes: Establishment and Reseeding of Viral Reservoirs Contributing to HIV-Associated Neurocognitive Disorders (Full text)

Mechanisms of CNS Viral Seeding by HIV+ CD14+ CD16+ Monocytes: Establishment and Reseeding of Viral Reservoirs Contributing to HIV-Associated Neurocognitive Disorders HIV reservoirs persist despite antiretroviral therapy (ART) and are established within a few days after infection. Infected myeloid cells in the central nervous system (CNS) may contribute to the establishment of a CNS viral reservoir. The mature CD14+ CD16+ monocyte subset enters the CNS in response to chemokines, including CCL2 (...) . Entry of infected CD14+ CD16+ monocytes may lead to infection of other CNS cells, including macrophages or microglia and astrocytes, and to release of neurotoxic early viral proteins and additional cytokines. This contributes to neuroinflammation and neuronal damage leading to HIV-associated neurocognitive disorders (HAND) in ~50% of HIV-infected individuals despite ART. We examined the mechanisms of monocyte entry in the context of HIV infection and report for the first time that HIV+ CD14+ CD16

2017 mBio PubMed

98. Neuroprotective effects of estrogen in CNS injuries: insights from animal models (Full text)

paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal (...) Neuroprotective effects of estrogen in CNS injuries: insights from animal models Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2) is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS) injuries such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic brain injury (IBI). These CNS injuries are not only serious health problems, but also enormous economic burden

2017 Neuroscience and neuroeconomics PubMed

99. Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected (Full text)

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection (...) remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able

2017 Acta neuropathologica communications PubMed

100. Route of antibiotic prophylaxis for prevention of cerebrospinal fluid-shunt infection. (PubMed)

Diseases of the CNS Group. The search was performed in January 2018.All randomised and quasi-randomised controlled trials that studied the effect of antibiotic prophylaxis, in any dose or administration route, for the prevention of CSF-shunt infection in patients that were treated with an internal cerebrospinal fluid shunt. Patients with external shunts were not eligible.Two review authors independently extracted data from included studies. We resolved disagreements by discussion or by referral (...) Route of antibiotic prophylaxis for prevention of cerebrospinal fluid-shunt infection. The main complication of cerebrospinal fluid (CSF) shunt surgery is shunt infection. Prevention of these shunt infections consists of the perioperative use of antibiotics that can be administered in five different ways: orally; intravenously; intrathecally; topically; and via the implantation of antibiotic-impregnated shunt catheters.To determine the effect of different routes of antibiotic prophylaxis (i.e

2019 Cochrane

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