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CNS Infection

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21. Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection (PubMed)

Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection Central nervous system (CNS) infection caused by Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited studies are available on CNS-TB animal model development. The present study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from (...) the cerebrospinal fluid (CSF) of CNS-TB patients.Groups of mice were infected by the intravenous route with MTB C3 strain isolated from the CSF of CNS-TB patients. Brain and lung tissue were evaluated for bacterial burden, histopathology and surrogate markers of TB infection at 30 and 50 days post-infection.Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease with high bacillary burden in lungs at the initial stage (30 days), which eventually disseminated to the brain

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2017 The Indian journal of medical research

22. Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice (PubMed)

Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 (...) constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1. In the present study, we found that the demyelination in macrophage-intact mice infected with HSV-IL-2 was blocked by depletion of FoxP3-expressing cells, while concurrent depletion of macrophages restored demyelination. In contrast, demyelination was blocked in the macrophage-depleted mice infected with wild-type HSV-1

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2017 PLoS pathogens

23. Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection (PubMed)

Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection Infiltration of infected leukocytes culminates in establishment of a brain niche for Human Immunodeficiency Virus (HIV) during acute phase of infection, initiating an ongoing cascade of persistent viral replication and inflammation, that causes irreversible neuronal injury and HIV associated neurocognitive disease (HAND). In this study, humanized mice were treated with Smoothened Agonist (SAG (...) of activated astrocytes. Additional in vitro experiments suggested SAG treatment was not associated with the establishment or reversal of latency in the target cells. Altogether, these findings validate neuroprotective role of Shh signaling and highlight the therapeutic potential of Shh mimetics against CNS complications associated with HIV infection. Further our results strongly demonstrate that pharmacological interventions to reduce leukocyte mobilization during early HIV infection, can provide

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2017 Scientific reports

24. Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines (PubMed)

Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines Rabies remains a major public health issue worldwide, especially in developing countries where access to medical care can represent a real challenge. While there is still no cure for rabies, it is a vaccine-preventable disease with pre- and post-exposure prophylaxis regimens approved by the World Health Organization (WHO). However, many rabies-exposed (...) immunity, superior to the protection induced by inactivated vaccines. In the absence of an immunostimulatory adjuvant, vaccination with multiple doses of inactivated rabies virus induces a type-2 immune response. This type of immunity is highly effective at inducing neutralizing antibody but has limited efficacy in clearing the virus from central nervous system (CNS) tissues. In contrast, a single infection with live-attenuated rabies vaccine safely drives a type-1 immune response, associated with both

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2017 Tropical Medicine and Infectious Disease

25. Protective and pathological immunity during CNS infections (PubMed)

Protective and pathological immunity during CNS infections The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological (...) inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege.Copyright © 2017. Published

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2017 Immunity

26. Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection (PubMed)

Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection Herpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological complications, involving behavioral and cognitive impairments that cause significant morbidity and a reduced quality of life. We showed that HSE results from dysregulated central nervous system (CNS) inflammatory responses. We hypothesized that CNS inflammation is casually involved in behavioral abnormalities after HSE and that treatment with ACV (...) and pooled human immunoglobulin (IVIG), an immunomodulatory drug, would improve outcomes compared to mice treated with phosphate buffered saline (PBS) or ACV alone. Anxiety levels were high in HSV-infected PBS and ACV-treated mice compared to mice treated with ACV + IVIG, consistent with reports implicating inflammation in anxiety induced by lipopolysaccharide (LPS) or stress. Female, but not male, PBS-treated mice were cognitively impaired, and unexpectedly, ACV was protective, while the inclusion

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2017 Behavioural neurology

27. Diverse Protein Profiles in CNS Myeloid Cells and CNS Tissue From Lipopolysaccharide- and Vehicle-Injected APPSWE/PS1ΔE9 Transgenic Mice Implicate Cathepsin Z in Alzheimer’s Disease (PubMed)

Diverse Protein Profiles in CNS Myeloid Cells and CNS Tissue From Lipopolysaccharide- and Vehicle-Injected APPSWE/PS1ΔE9 Transgenic Mice Implicate Cathepsin Z in Alzheimer’s Disease Neuroinflammation, characterized by chronic activation of the myeloid-derived microglia, is a hallmark of Alzheimer's disease (AD). Systemic inflammation, typically resulting from infection, has been linked to the progression of AD due to exacerbation of the chronic microglial reaction. However, the mechanism (...) of the hippocampus from the same mice as well as in unique samples of CNS myeloid cells. The repeated LPS injections stimulated protein pathways of the complement system, retinoid receptor activation and oxidative stress. CNS myeloid cells from transgenic mice showed enrichment in pathways of amyloid-beta clearance and elevated levels of the lysosomal protease cathepsin Z, as well as amyloid precursor protein, apolipoprotein E and clusterin. These proteins were found elevated in the proteome of both LPS

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2018 Frontiers in cellular neuroscience

28. HIV-1 RNA Detected in the CNS after Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. (PubMed)

over 3 years of ART. CSF escape in two other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART, but that CSF escape is not exclusively produced by a replicating CNS reservoir. (...) HIV-1 RNA Detected in the CNS after Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells. HIV-1 populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs.We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross

2018 Clinical Infectious Diseases

29. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study

Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study The prognosis for primary CNS lymphoma has improved with the use of high-dose methotrexate-based chemotherapy, but patient outcomes remain poor. Rituximab, a chimeric monoclonal antibody that targets the CD20 cell surface protein, has substantial activity in systemic CD20-positive diffuse large B-cell lymphoma, but its efficacy in primary CNS lymphoma is unknown and low (...) penetration of the large rituximab molecule through the blood-brain barrier could limit its effect. We aimed to investigate the addition of rituximab to a high-dose methotrexate-based chemotherapy regimen in patients with newly diagnosed primary CNS lymphoma.This intergroup, multicentre, open-label, randomised phase 3 study was done at 23 hospitals in the Netherlands, Australia, and New Zealand. Non-immunocompromised patients aged 18-70 years with newly diagnosed primary CNS lymphoma were randomly

2019 EvidenceUpdates

30. Role of beta-2-microglobulin as a biomarker in very preterm and extremely preterm infants with CNS inflammation. (PubMed)

Role of beta-2-microglobulin as a biomarker in very preterm and extremely preterm infants with CNS inflammation. Premature infants are at risk for severe sepsis and meningitis, both infections associated with high mortality and morbidity. Cerebro-spinal fluid (CSF) culture is the gold standard method for meningitis diagnosis, but interpretation of biochemical parameters of CSF is essential at the moment of the analysis in order to start the appropriate treatment. The main objective (...) of this study was to determine whether levels of CSF beta-2-microglobulin (B2M) were elevated in preterm infants with CNS infections or other inflammatory processes, and to establish if there were differences in B2M concentrations amongst various inflammatory settings (sepsis, meningitis, and progressive post-hemorrhagic ventricular dilatation (PHVD)).This is a retrospective study of all very preterm and extremely preterm infants (< 32 weeks of gestation) admitted to our NICU between 2012 and 2017. All

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2019 PLoS ONE

31. Non-human primate models of SIV infection and CNS neuropathology (PubMed)

Non-human primate models of SIV infection and CNS neuropathology Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each (...) of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages. Consistent in all of these models are data underscoring the importance of monocyte and macrophage activation, infection and accumulation in the CNS.Copyright © 2016 Elsevier B.V. All rights reserved.

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2016 Current opinion in virology

32. IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection (PubMed)

IL-10 plays an important role in the control of inflammation but not in the bacterial burden in S. epidermidis CNS catheter infection Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection.In this study, a murine model of catheter (...) -associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 knockout (IL-10 knockout) mice. Bacterial titers as well as cytokine and chemokine levels were measured at days 3, 5, 7, and 10 in mice implanted with sterile and S

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2016 Journal of neuroinflammation

33. CNS Infection

CNS Infection CNS Infection Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 CNS Infection CNS Infection Aka: CNS Infection From (...) Related Chapters Images: Related links to external sites (from Bing) These images are a random sampling from a Bing search on the term "CNS Infection." Click on the image (or right click) to open the source website in a new browser window. Related Studies (from Trip Database) Ontology: Central Nervous System Infection (C0007684) Definition (NCI) An infectious process that affects the brain and/or spinal cord. Representative examples include encephalitis, poliomyelitis, arachnoiditis, and meningitis

2018 FP Notebook

34. Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice (PubMed)

Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently (...) expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.

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2016 PLoS pathogens

35. Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection (PubMed)

Blood-CSF barrier and compartmentalization of CNS cellular immune response in HIV infection HIV infection is persistent in the CNS, to evaluate the compartmentalization of the CNS immune response to HIV, we compared soluble markers of cellular immunity in the blood and CSF among HIV- (n=19) and HIV+ (n=68), as well as among HIV participants with or without CSF pleocytosis. Dysfunction of the blood cerebrospinal fluid barrier (BCSFB) was common in HIV participants. CSF levels of TNFα, IFNγ, IL-2 (...) , IL-6, IL-7, IL-10, IP-10, MIP-1α, MIP-1β, and RANTES were significantly higher in participants with CSF pleocytosis (P<0.05); serum levels of these biomarkers were comparable. The CNS immune response is compartmentalized, and remains so despite the BCSFB dysfunction during HIV infection; it is markedly reduced by virology suppression, although BCSFB dysfunction persists on this subgroup.Copyright © 2016 Elsevier B.V. All rights reserved.

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2016 Journal of Neuroimmunology

36. CNS Impact of Perinatal HIV Infection and Early Treatment: The Need for Behavioral Rehabilitative Interventions Along with Medical Treatment and Care (PubMed)

CNS Impact of Perinatal HIV Infection and Early Treatment: The Need for Behavioral Rehabilitative Interventions Along with Medical Treatment and Care There is growing concern that although the more severe forms of HIV-associated neurologic deficits are reduced following highly active anti-retroviral therapy (HAART), mild to moderate cognitive disorders may persist for years after HAART initiation and this may occur despite complete plasma viral suppression. According to the UNAIDS 2014 report

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2016 Current HIV/AIDS reports

37. CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors (PubMed)

CNS autoimmune disease after Streptococcus pyogenes infections: animal models, cellular mechanisms and genetic factors Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham's chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several (...) factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met

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2016 Future Neurology

38. Recurrent Transcortical Motor Aphasia—Another CNS Infectious Syndrome Associated with Herpes Virus Infection (PubMed)

Recurrent Transcortical Motor Aphasia—Another CNS Infectious Syndrome Associated with Herpes Virus Infection Herpes simplex encephalitis is an acute/subacute illness that causes both general and focal signs of cerebral dysfunction with fever, headache, and confusion as cardinal features. Recurrent herpes simplex meningitis, also known as Mollaret's meningitis, is another manifestation of central nervous system herpetic infection with recurrent episodes of fever, headache, and nuchal rigidity (...) associated with cerebrospinal fluid (CSF) evidence of active herpes simplex infection. Bell's palsy is yet another manifestation of a herpes virus infection in at least some reported cases documented by CSF analysis. We report a case of a 70-year-old male who presented with acute transcortical motor aphasia initiating a stroke work-up that was negative. Physical examination revealed genital vesicles, and the CSF was consistent with active herpes simplex infection.

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2016 Journal of vascular and interventional neurology

39. Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection (PubMed)

Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection Despite the significant advances in neurological medicine, it remains difficult to treat ailments directly involving the brain. The blood brain barrier (BBB) is a tightly regulated, selectively permeable barrier that restricts access from the blood into the brain extracellular fluid (BEF). Many conditions such as tumors or infections in the brain are difficult to treat due to the fact that drugs and other therapeutic

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2016 Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

40. CNS infections in patients with hematological disorders (including allogeneic stem cell transplantation) -Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). (PubMed)

CNS infections in patients with hematological disorders (including allogeneic stem cell transplantation) -Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell (...) transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying

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2016 Annals of Oncology

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