A5017847129- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Autoimmune Neurological Disorders and Treatments
- Immune cells in cancer
- Multiple Sclerosis Research Studies
- interferon and immune responses
- Single-cell and spatial transcriptomics
- Cellular transport and secretion
- Peripheral Neuropathies and Disorders
- Immune Cell Function and Interaction
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
- Neurogenesis and neuroplasticity mechanisms
- Animal Virus Infections Studies
- RNA regulation and disease
- Genetic Neurodegenerative Diseases
- HIV Research and Treatment
- Long-Term Effects of COVID-19
- Neuroscience and Neuropharmacology Research
- Molecular Biology Techniques and Applications
- Pharmacological Effects and Toxicity Studies
- Tryptophan and brain disorders
- Barrier Structure and Function Studies
Mayo Clinic in Arizona
2016-2025
Institute of Neuroimmunology of the Slovak Academy of Sciences
2023
Mayo Clinic
2017-2022
WinnMed
2017-2022
University of Wisconsin–Madison
2010-2017
Neurological Surgery
2014
<h3>Importance</h3> Recognizing the presenting and immunopathological features of Kelch-like protein-11 immunoglobulin G seropositive (KLHL11 IgG+) patients may aid in early diagnosis management. <h3>Objective</h3> To describe expanding neurologic phenotype, cancer associations, outcomes, immunopathologic KLHL11 encephalitis. <h3>Design, Setting, Participants</h3> This retrospective tertiary care center study, conducted from October 15, 1998, to November 1, 2019, prospectively identified 31...
Abstract Cellular senescence is a plausible mediator of inflammation-related tissue dysfunction. In the aged brain, senescent cell identities and mechanisms by which they exert adverse influence are unclear. Here we used high-dimensional molecular profiling, coupled with mechanistic experiments, to study properties cells in mouse brain. We show that inflammatory expression profiles increase age brain region- sex-specific. p16 -positive myeloid exhibiting disease-associated activation...
T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but relevant cell–derived mediators tissue injury remain unknown. Using a mouse model transient focal brain ischemia, we report that IL-21 is highly up-regulated in injured after ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation within 24 h reperfusion. Intracellular cytokine staining adoptive transfer experiments revealed...
We recently reported successful treatment of a child with febrile infection-related epilepsy syndrome (FIRES), subtype new onset refractory status epilepticus, the recombinant interleukin-1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.Levels IL1β and were measured serum cerebrospinal fluid (CSF). The inhibitory activity was assessed using cell-based reporter assay. IL1RN gene variants...
Central nervous system (CNS) immune privilege is complex and it still not understood how CNS antigens are sampled by the peripheral under steady state conditions. To compare antigen sampling from immune-privileged or nonprivileged tissues, we created transgenic mice with oligodendrocyte gut epithelial cell expression of an EGFP-tagged fusion protein containing ovalbumin (OVA) antigenic peptides tested anti-OVA peptide-specific sentinel OT-I OT-II T activation. We report that similarly, as...
Dendritic cells (DCs)--although absent from the healthy CNS parenchyma--rapidly accumulate within brain and spinal cord tissue during neuroinflammation associated with experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis). Yet, although DCs have been appreciated for their role in initiating adaptive immune responses peripheral lymphoid organ tissues, how infiltrate contribute to ongoing situ is poorly understood. In this study, we report following: 1) CD11c(+)...
Abstract Dendritic cells (DC) accumulate in the CNS during neuroinflammation, yet, how these contribute to antigen drainage is still unknown. We have previously shown that after intracerebral injection, antigen-loaded bone marrow DC migrate deep cervical lymph nodes where they prime antigen-specific T and exacerbate experimental autoimmune encephalomyelitis (EAE) mice. Here, we report migration from brain parenchyma dependent upon chemokine receptor CCR7. During EAE, both wild type CCR7−/−...
Objective This study was undertaken to describe a novel biomarker of germ cell tumor and associated paraneoplastic neurological syndrome (PNS). Methods Archival sera from patients with tumor–associated PNS were evaluated. We identified common autoantigen in human testicular cancer line (TCam‐2) by Western blot mass spectrometry. Its identity confirmed recombinant‐protein blot, enzyme‐linked immunosorbent assay (ELISA), cell‐based assay. Autoantibody specificity analyzing assorted control...
Abstract Background The pathogenic contribution of neuroinflammation to ictogenesis and epilepsy may provide a therapeutic target for reduction seizure burden in patients that are currently underserved by traditional anti-seizure medications. Theiler's murine encephalomyelitis virus (TMEV) model has provided important insights into the role inflammation ictogenesis, but questions remain regarding relative microglia inflammatory monocytes this model. Methods Female C57BL/6 mice were...
During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes network hyperexcitability. Indeed, inflammatory are implicated dysfunction epilepsy and an array degenerative autoimmune diseases central nervous system. Current tools for studying impact factors on neural networks either insufficiently fast sensitive or require complicated costly experimental rigs. Calcium imaging offers a reasonable...
ABSTRACT Inflammatory response of blood–brain barrier (BBB) endothelial cells plays an important role in pathogenesis many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB cell remains unclear. In this study, we first observed that knockdown neuropilin-1 (NRP1), a co-receptor several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation STAT1 brain...
We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects.Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue cell based) or Western blot. binding (and internalization of) extracellular epitopes evaluated live rat hippocampal neuron assay. The impact purified patient IgGs on murine cortical function was determined recording field potentials in a multielectrode array platform.Septin-IgGs identified 23...
Abstract Astrocytes utilize both glycolytic and mitochondrial pathways to power cellular processes that are vital maintaining normal CNS functions. These cells also mount inflammatory acute phase reactive programs in response diverse stimuli. While the metabolic functions of astrocytes under homeostatic conditions well-studied, role bioenergetics astrocyte reactivity is poorly understood. Teriflunomide exerts immunomodulatory effects diseases such as multiple sclerosis by metabolically...
CD8+ T cells outnumber CD4+ in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally expanded effectors are unknown. Based on evidence that demyelination is necessary not sufficient for progression MS, we previously hypothesized CNS-infiltrating specific neuronal antigens directly drive axonal injury leads to cumulative neurologic disability patients MS. We now show induced expression MHC class I neurons axons...
The causes of grey matter pathology and diffuse neuron injury in MS remain incompletely understood. Axonal stress signals arising from white lesions has been suggested to play a role initiating this pathology. Therefore, identify the most upstream transcriptional responses neurons demyelinated axons, we analyzed transcriptome actively translating neuronal transcripts mouse models demyelinating disease. Among upregulated genes, identified associated with ISGylation pathway. refers covalent...
Abstract Objective Injury‐associated axon‐intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory neurodegenerative diseases, including multiple sclerosis ( MS ). Retrograde interferon gamma IFN γ ) known induce expression of major histocompatibility class I MHC I) genes murine axons, thereby increasing the susceptibility these axons attack by antigen‐specific CD 8 + T cells. We sought determine whether same is true human neurons. Methods A novel...
We sought to develop medium throughput standard operating procedures for screening cryopreserved human peripheral blood mononuclear cells (PBMCs) CD4+ and CD8+ T cell responses potential autoantigens. Dendritic were loaded with a peptide cocktail from ubiquitous viruses or full-length viral protein antigens cocultured autologous cells. measured expression of surface activation markers on by flow cytometry time flight 24–72 h later. tested among freshly isolated healthy control PBMCs, cells,...