A5023657168- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- Gut microbiota and health
- Alzheimer's disease research and treatments
- Acute Ischemic Stroke Management
- Bladder and Urothelial Cancer Treatments
- Pelvic floor disorders treatments
- Atherosclerosis and Cardiovascular Diseases
- Immune Response and Inflammation
- Urinary Tract Infections Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Tryptophan and brain disorders
- Immune cells in cancer
- Traumatic Brain Injury and Neurovascular Disturbances
- Advanced Glycation End Products research
- Chemical Reaction Mechanisms
- Urinary and Genital Oncology Studies
- Urinary Bladder and Prostate Research
- Cardiovascular and Diving-Related Complications
- Olfactory and Sensory Function Studies
- Functional Brain Connectivity Studies
- Neurological Disorders and Treatments
- S100 Proteins and Annexins
- Neural dynamics and brain function
- Amyotrophic Lateral Sclerosis Research
Ludwig-Maximilians-Universität München
2005-2025
LMU Klinikum
2014-2024
Munich Cluster for Systems Neurology
2014-2019
Roth and Rau (Germany)
2018
Witten/Herdecke University
2003-2017
Helios Universitätsklinikum Wuppertal
2005-2017
IFT Institut für Therapieforschung
2015
Klinik und Poliklinik für Urologie
1993
University of Münster
1993
Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested key role of gut microbiota in autoimmune diseases by modulating homeostasis. Therefore, we investigated mechanistic link among acute ischemia, alterations, response after injury. Using two distinct models middle cerebral artery occlusion, show next-generation sequencing that large stroke lesions cause dysbiosis, which turn affects outcome...
Acute brain lesions induce profound alterations of the peripheral immune response comprising opposing phenomena early activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental ischemia as a paradigm acute additionally investigated large cohort stroke patients. inflammatory potency HMGB1 its pathways by immunological in vivo vitro techniques. Features complex behavioral sickness behavior...
Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on outcome. However, mechanisms underlying gut–brain interaction implications for long-term recovery are largely elusive. Here, we tested hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, missing link along axis might be able to modulate experimental stroke. SCFA...
Numerous treatments have been reported to provide a beneficial outcome in experimental animal stroke models; however, these (with the exception of tissue plasminogen activator) failed clinical trials. To improve translation treatment efficacy from bench bedside, we performed preclinical randomized controlled multicenter trial (pRCT) test potential therapy under circumstances closer design and rigor control trial. Anti-CD49d antibodies, which inhibit migration leukocytes into brain, were...
Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, mechanisms microbiome–brain interaction AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) mice exhibit substantially reduced plaque load and markedly SCFA plasma concentrations; conversely, supplementation to GF increased levels conventionally colonized...
The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized these might share a common immunological cause, yet effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as cause remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages multiple organs up to 3 months...
The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly in patients with atherosclerosis, more than 10% experiencing events1,2. However, the enormous medical burden this clinical phenomenon, underlying mechanisms leading to increased vascular and are largely unknown. Here, using a novel mouse model stroke-induced ischaemia, we show that leads activation AIM2 inflammasome vulnerable atherosclerotic...
Microbiome alterations have been shown to affect stroke outcome. However, what extent the presence of a gut microbiome per se is affecting post-stroke neuroinflammation has not tested. By comparing germfree mice with recolonized (Ex-GF) and conventional SPF mice, we were able demonstrate that bacterial colonization reduces volumes. Bacterial increased cerebral expression cytokines as well microglia/macrophage cell counts in contrast improved Interestingly, microbiome-mediated brain...
Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little known about proteome-wide changes in microglia during the course AD and their functional consequences. Here, we performed an in-depth time-resolved proteomic characterization two mouse models amyloid β (Aβ) pathology, overexpression APPPS1 knock-in APP-NL-G-F (APP-KI) model. We identified large panel Aβ Response Proteins (MARPs) that reflect heterogeneity microglial alterations early, middle advanced...
Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role HDAC (histone deacetylase)-9 in and its clinical complications including stroke myocardial infarction. To determine mechanisms linking HDAC9 to these vascular pathologies explore therapeutic potential for atheroprotection. We studied effects Hdac9 on features plaque vulnerability using bone marrow reconstitution experiments...
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental deep learning pipeline comprehensively quantify the targeting nanocarriers throughout mouse body at single-cell resolution. SCP-Nano reveals tissue distribution patterns lipid nanoparticles (LNPs) after different...
Recent studies reported an increased prevalence of patent foramen ovale (PFO) in patients with migraine aura (MA+). To investigate the possible relationship between MA+ and paradoxical embolism, we studied both conditions. Investigation PFO was undertaken 74 consecutive presenting acute stroke undetermined origin. The were questioned about or without (MA–) according to criteria International Headache Society. Follow-up performed evolution MA– different treatments stroke. found 44 patients,...
Stroke is the third most common cause of death and a main acquired adult disability in developed countries. Only very limited therapeutical options are available for small proportion stroke patients acute phase. Current research intensively searching novel therapeutic strategies increasingly focusing on sub-acute chronic phase after because more might be eligible interventions prolonged time window. These delayed mechanisms include important pathophysiological pathways such as post-stroke...
Stroke induces a multiphasic systemic immune response, but the consequences of this response on atherosclerosis-a major source recurrent vascular events-have not been thoroughly investigated. We show that stroke exacerbates atheroprogression via alarmin-mediated propagation inflammation. The prototypic brain-released alarmin high-mobility group box 1 protein induced monocyte and endothelial activation receptor for advanced glycation end products (RAGE)-signaling cascade increased plaque load...
The organization of brain areas in functionally connected networks, their dynamic changes, and perturbations disease states are subject extensive investigations. Research on functional networks humans predominantly uses magnetic resonance imaging (fMRI). However, adopting fMRI other methods to mice, the most widely used model study physiology disease, poses major technical challenges faces important limitations. Hence, there is great demand for alternative modalities network...
Cytoplasmic aggregation and concomitant nuclear clearance of the RNA-binding protein TDP-43 are found in ~ 90% cases amyotrophic lateral sclerosis 45% patients living with frontotemporal lobar degeneration, but no disease-modifying therapy is available. Antibody targeting other aggregating proteins associated neurodegenerative disorders has shown beneficial effects animal models clinical trials. The most effective epitopes for safe antibody unknown. Here, we identified active potential...
Experimental stroke models producing clinically relevant functional deficits are often associated with high mortality. Because the mechanisms that underlie post-stroke mortality largely unknown, results obtained using these difficult to interpret, thereby limiting their translational potential. Given specific forms of care reduce in patients, we hypothesized inadequate food and water intake may following experimental stroke. C57BL/6 mice were subjected 1 h intraluminal filament middle...
Report20 December 2019Open Access Source DataTransparent process Active poly-GA vaccination prevents microglia activation and motor deficits in a C9orf72 mouse model Qihui Zhou orcid.org/0000-0001-5733-9820 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Munich Cluster of Systems Neurology (SyNergy), Search more papers by this author Nikola Mareljic Meike Michaelsen Samira Parhizkar Chair Metabolic Biochemistry, Biomedical (BMC), Faculty Medicine,...
Testicular intraepithelial neoplasia (TIN) of the testis is noninvasive precursor testicular germ cell tumours (GCT) and can be detected by a single random biopsy in 5% patients with GCT contralateral testes. Although it generally presumed that TIN dispersed throughout testis, we realize about 60% bearing tissue close to its distribution not homogenously diffuse, but may focal. Thus tested whether improve diagnostic safety detecting increasing number biopsies. We could finally evaluate 295...
Physiological polyamines are required in various biological processes. In the current study, we used norspermidine, a structural analog of natural polyamine spermidine, to investigate uptake model organism Caenorhabditis elegans. Norsper-midine was found have two remarkable effects: it is toxic for nematode, without affecting its food, Escherichia coli; and hampers RNA interference. By characterizing norspermidine-resistant C. elegans mutant strain that has been isolated genetic screen,...
Urinary retention is a common emergency requiring immediate catheterization. Gradual decompression (GD) of the extended bladder believed to minimize risk complications such as bleeding or circulatory collapse, but date it has not been compared with rapid (RD) in controlled trials.Male patients presenting urinary (n = 294) were randomized gradual For latter, transurethral catheter was clamped for 5 min after every 200-ml outflow until completely empty. Patients monitored at least 30...
Lost control: The rationalization of the ambident reactivity NO2− by change between charge control to orbital has be revised. SN1-type reactions carbocations with give kinetically controlled product mixtures only when these proceed without activation energy (diffusion control). Activation-controlled SN1 alkylations are reversible and lead thermodynamically more stable nitro compounds. Supporting information for this article is available on WWW under...
Abstract Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction subsequent neuroinflammation. However, the relationship between these processes remains elusive. In current study, we investigated whether alleviating restoring nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized cyclic guanosine monophosphate (cGMP) levels, reduced elevated expression...