A5088146082- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Angiogenesis and VEGF in Cancer
- Radiomics and Machine Learning in Medical Imaging
- Cell death mechanisms and regulation
- Histone Deacetylase Inhibitors Research
- Barrier Structure and Function Studies
- RNA modifications and cancer
- Acute Ischemic Stroke Management
- Neurological Disease Mechanisms and Treatments
- Ion channel regulation and function
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Neurological disorders and treatments
- Phagocytosis and Immune Regulation
- Memory and Neural Mechanisms
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- Zebrafish Biomedical Research Applications
Charité - Universitätsmedizin Berlin
2015-2024
German Centre for Cardiovascular Research
2020-2024
University of Hong Kong
2024
Humboldt-Universität zu Berlin
2001-2024
Freie Universität Berlin
2018-2024
Einstein Center for Neurosciences Berlin
2020-2024
University of North Carolina at Chapel Hill
2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2016-2023
Institute of Experimental Endocrinology of the Slovak Academy of Sciences
2001-2016
Neurology, Inc
2016
Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves endothelium function, and protects from vascular disease. Here, we tested whether voluntary running would enhance neovascularization long-term recovery following mild brain ischemia. Wild-type mice were exposed to 30 minutes of middle-cerebral artery occlusion (MCAo) reperfusion. Continuous on wheels conferred upregulation eNOS in the vasculature progenitor cells (EPCs) spleen bone marrow (BM). This was...
Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell necrosis. Deletion or inhibition of PARP protects against ischemic brain injury. Here we examined neuroprotective effect PJ34, a novel potent inhibitor in vitro vivo. Serum-free primary neuronal cultures derived from rat cortex (E15-17) kept culture for 10 days were exposed oxygen glucose deprivation (OGD) vitro. Neuronal injury was...
After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute apoptosis in various conditions including ischemia. We demonstrate that loss endogenous cyclin-dependent kinase (Cdk) inhibitor p16 INK4a an early and reliable indicator death striatal after cerebral ischemia vivo . Loss p27 Kip1 , another Cdk inhibitor, precedes neocortical subjected oxygen–glucose deprivation vitro The inhibitors followed by...
Abstract Statins [3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors] exert cholesterol‐independent pleiotropic effects that include anti‐thrombotic, anti‐inflammatory, and anti‐oxidative properties. Here, we examined direct protective of atorvastatin on neurones in different cell damage models vitro . Primary cortical were pre‐treated with then exposed to (i) glutamate, (ii) oxygen–glucose deprivation or (iii) several apoptosis‐inducing compounds. Atorvastatin...
Small ubiquitin-like modifier (SUMO)2/3 but not SUMO1 conjugation is activated after transient cerebral ischemia. To investigate its function, we blocked neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary cortical neurons. Viability was unaffected by silencing unless neurons were stressed oxygen–glucose deprivation (OGD). Both 15 and 45 minutes of OGD tolerated control microRNA-expressing damaged >60% expressing microRNA. Damaging (75 minutes) increased loss to...
Abstract Background DNA methylation‐based classification of cancer provides a comprehensive molecular approach to diagnose tumours. In fact, methylation profiling human brain tumours already profoundly impacts clinical neuro‐oncology. However, current implementation using hybridisation microarrays is time consuming and costly. We recently reported on shallow nanopore whole‐genome sequencing for rapid cost‐effective generation genome‐wide 5‐methylcytosine profiles as input supervised...
The major goal of this study was to compare mechanisms the neuroprotective potential 17 β-estradiol in two models for oxidative stress-independent apoptotic neuronal cell death with that necrotic primary cultures derived from rat hippocampus, septum, or cortex. Neuronal apoptosis induced either by staurosporine ethylcholine aziridinium (AF64A), as glutamate exposure oxygen–glucose deprivation (OGD) were applied. Long-term (20 hr) pretreatment (0.1 μ m β-estradiol) AF64A (40 ) only...
Folate deficiency and resultant increased homocysteine levels have been linked experimentally epidemiologically with neurodegenerative conditions like stroke dementia. Moreover, folate has implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that pathogenic mechanisms include uracil misincorporation and, therefore, analyzed effects mice lacking DNA glycosylase ( Ung −/−) versus wild-type controls. depletion nuclear mutation rates −/− embryonic...
Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals angiogenesis. It was the aim this study determine its function in poststroke outcome.We generated tamoxifen-inducible endothelial-specific Stat3 knockout mouse model by crossbreeding Stat3(floxed/KO) Tie2-Cre(ERT2) mice. Cerebral ischemia induced 30 minutes middle cerebral artery occlusion. We demonstrated that...
Lesion volume measurements with magnetic resonance imaging are widely used to assess outcome in rodent models of stroke. In this study, we improved a mathematical framework correct lesion size for edema which is based on manual delineation the and hemispheres. Furthermore, novel MATLAB toolbox register mouse brain MR images Allen atlas presented. Its capability calculate edema-corrected was compared approach. Automated image registration performed equally well middle cerebral artery...
Activation of the endothelium is a pivotal first step for leukocyte migration into diseased brain. Consequently, imaging this activation process highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance revealed targeted accumulated in brain vasculature following acute administration clinically relevant animal model stroke, though increases selectin...
Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive tumor-supportive phenotype in these glioma-associated microglia/brain (GAMs). A subpopulation of glioma cells acts as stem (GSCs). We explored interaction between GSCs GAMs. Using CD133 a marker stemness, we enriched for or deprived mouse cell line GL261 by fluorescence-activated sorting (FACS). Over same period time, 100 CD133+ had capacity to form...
Reduced expression of the Indy (“I am Not Dead, Yet”) gene in lower organisms promotes longevity a manner akin to caloric restriction. Deletion mammalian homolog ( mIndy, Slc13a5 ) encoding for plasma membrane–associated citrate transporter expressed highly liver, protects mice from high‐fat diet–induced and aging‐induced obesity hepatic fat accumulation through mechanism resembling We studied possible role mIndy human metabolism. In obese, insulin‐resistant patients with nonalcoholic fatty...
Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, phenotypically normal have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase the uracil/cytosine ratio genome augmented cell death. After combined oxygen-glucose deprivation, primary cortical neurons increased vulnerability death, which associated...
Since pharmacological interactions of the renin-angiotensin system appear to alter neurological outcome stroke patients significantly, we examined effect elevated levels angiotensin II and role its receptor subtype AT1 in brain infarction transgenic mice after focal cerebral ischemia. Angiotensinogen-overexpressing knockout underwent 1 h or 24 permanent middle artery occlusion (MCAO). The current study revealed a much smaller penumbra size, i.e., tissue at risk,...
Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, phenotypically normal have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase the uracil/cytosine ratio genome augmented cell death. After combined oxygen-glucose deprivation, primary cortical neurons increased vulnerability death, which associated...
A strictly anaerobic, Gram-positive, non-spore-forming bacterium was isolated from sewage sludge which grew on creatinine as sole source of carbon and energy. This new isolate, designated strain KRE 4T, totally degraded via creatine, sarcosine glycine to the products acetate, monomethylamine, ammonia dioxide. Growth or creatine selenium-dependent stimulated by formate, indicating involvement a reductase, reductase and/or reductase. substantiated fact that were reduced cell-free extracts....
The role of glucocorticoids in the regulation apoptosis remains incongruous. Here, we demonstrate that corticosterone protects neurons from by a mechanism involving cyclin-dependent kinase inhibitor p21 Waf1/Cip1 . In primary cortical neurons, leads to dose- and Akt-kinase-dependent upregulation with enhanced phosphorylation cytoplasmic appearance at Thr 145. Exposure neurotoxin ethylcholine aziridinium (AF64A) results activation caspase-3 dramatic loss preceding neurons. These effects AF64A...
Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and proliferation. Identification regulatory proteins that control switch between apoptotic alternative DR opens new therapeutic opportunities. Fas inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor Fas/CD95-mediated apoptosis. To investigate its role during...