A5065867369- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Long-Term Effects of COVID-19
- Meningioma and schwannoma management
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Liver Diseases and Immunity
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Head and Neck Surgical Oncology
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Immune Response and Inflammation
- CAR-T cell therapy research
- Circadian rhythm and melatonin
- Cell Image Analysis Techniques
- Radiomics and Machine Learning in Medical Imaging
- Cerebrospinal fluid and hydrocephalus
- Optical Imaging and Spectroscopy Techniques
- Neurogenesis and neuroplasticity mechanisms
- interferon and immune responses
- Bioinformatics and Genomic Networks
- COVID-19 diagnosis using AI
University Medical Center Freiburg
2020-2024
University of Freiburg
2016-2024
Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent COVID-19, gains access to and causes neuropathological changes. We investigated brain tissue patients who died from for glial responses, inflammatory changes, presence SARS-CoV-2 in CNS.In this post-mortem case series, we features brains between March 13 April 24, 2020, Hamburg, Germany. Inclusion criteria...
Low-grade inflammation is a hallmark of old age and central driver ageing-associated impairment disease1. Multiple factors can contribute to inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling their impact in natural ageing remain unclear. Here we show cGAS-STING pathway, which mediates immune sensing DNA3, critical chronic functional decline during ageing. Blockade STING suppresses phenotypes senescent human cells tissues, attenuates ageing-related...
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into focus of interest. In this prospective cohort study, we assessed and cognitive in hospitalized disease-19 (COVID-19) patients aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because non-neurological complications were screened between 20 April 2020 12 May...
Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source reorganization within spatial context these remains elusive. Here, we characterized glioblastomas spatially resolved transcriptomics, metabolomics, proteomics. By deciphering regionally shared transcriptional programs across patients, infer that glioblastoma is organized segregation lineage states adapts to inflammatory and/or...
Single-cell analysis of CNS interactions Despite their importance in the physiology and pathology central nervous system (CNS), few methods are available for unbiased, systematic investigation cell-to-cell at single-cell resolution. Clark et al. developed RABID-seq, a method that combines barcoded viral tracing with RNA sequencing (see Perspective by Silvin Ginhoux). RABID-seq identified axon guidance molecules Sema4D-PlexinB2 EphrinB3-EphB3 as mediators microglia-astrocyte promote...
Significance In spite of TNF involvement in the pathogenesis multiple sclerosis (MS), systemic neutralization MS patients was not successful. One possible reasons is that possesses both pathogenic and protective features may be related to TNFR1 versus TNFR2 receptor engagement. This study uncovers one such functions mediated by intrinsic signaling T reg cells. mice bearing humanized genetic loci, ablation restricted cells led reduced capacity control Th17 cell responses, exacerbated...
Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) linked to severe neurological manifestations. Senescent cells contribute brain aging, but the impact of virus-induced senescence on neuropathologies unknown. Here we show that senescent accumulate in aged human organoids senolytics reduce age-related inflammation rejuvenate transcriptomic aging clocks. In postmortem brains patients with COVID-19 observed increased cell accumulation compared...
Background Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The accompanied by an abnormal deposition of ß-amyloid plaques in brain that contributes to neurodegeneration known induce glial inflammation. Studies APP/PS1 mouse model ß-amyloid-induced neuropathology have suggested a role for inflammasome activation neuroinflammation neuropathology. Methods Here, we evaluated vivo microglia-selective full body signalling several models AD...
Cancer treatment with anti-PD-1 immunotherapy can cause central nervous system immune-related adverse events (CNS-irAEs). The role of microglia in immunotherapy-induced CNS-irAEs is unclear. We found that mice caused morphological signs activation and major histocompatibility complex (MHC) class II up-regulation on microglia. Functionally, induced neurocognitive deficits mice, independent T cells, B natural killer cells. Instead, we mediated these CNS-irAEs. Single-cell RNA sequencing...
Homo and heterozygote cx3cr1 mutant mice, which harbor a green fluorescent protein (EGFP) in their loci, represent widely used animal model to study microglia peripheral myeloid cells. Here we report that the dentate gyrus (DG) of −/− mice displayed elevated microglial sirtuin 1 (SIRT1) expression levels nuclear factor kappa-light-chain-enhancer activated B cells (NF-kB) p65 activation, despite unaltered morphology when compared +/− or +/+ controls. This phenotype was restricted DG...
Abstract While the precise processes underlying a sex bias in development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to disease pathogenesis. When we mimicked systemic viral infection or applied murine cytomegalovirus (MCMV) systemically neonatal female and male mice, only adolescent mice presented behavioral deficits, including reduced social behavior cognition. This was paralleled by increased amount...
BACKGROUND AND OBJECTIVES: To systematically describe pertinent, intraoperative anatomic findings encountered when approaching spinal cerebrospinal fluid (CSF) leaks and CSF-venous fistulas in spontaneous intracranial hypotension (SIH). METHODS: In a retrospective study, we included surgically treated patients suffering from SIH at our institution April 2018 to March 2022. Anatomic, data were extracted operative notes supplemented with surgical videos images. Prominent features compared...
Nuclear pore complexes (NPCs) are highly dynamic macromolecular protein structures that facilitate molecular exchange across the nuclear envelope. Aberrant NPC functioning has been implicated in neurodegeneration. The translocated promoter region (Tpr) is a critical scaffolding nucleoporin (Nup) of basket, facing interior NPC. However, role Tpr adult neural stem/precursor cells (NSPCs) Alzheimer's disease (AD) unknown. Using super-resolution (SR) and electron microscopy, we defined different...
Abstract COVID-19 causes neurological symptoms that can be potentially life-threatening in up to 67 % of the patients. The underlying pathophysiological mechanisms associated encephalopathy, involved immune cells, their spatial distribution and cellular interactions during disease remain largely unclear. In this study, we performed a 38-biomarker imaging mass cytometry analysis brain stem from 25 patients additional controls understand local response SARS-CoV-2 infection at spatially...
The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared healthy controls, individuals revealed a high percentage TMEM119