A5051729685- Bacterial Infections and Vaccines
- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- Neuroscience and Neuropharmacology Research
- Nitric Oxide and Endothelin Effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
- Mitochondrial Function and Pathology
- Neonatal Respiratory Health Research
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Cell death mechanisms and regulation
- Electrochemical sensors and biosensors
- Barrier Structure and Function Studies
- Erythropoietin and Anemia Treatment
- Platelet Disorders and Treatments
- Trace Elements in Health
- Cellular Mechanics and Interactions
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Microtubule and mitosis dynamics
- Animal testing and alternatives
- Neurotransmitter Receptor Influence on Behavior
- Glioma Diagnosis and Treatment
Charité - Universitätsmedizin Berlin
2005-2020
Humboldt-Universität zu Berlin
1997-2018
Freie Universität Berlin
2017
Klinik und Poliklinik für Neurologie
2010-2013
Humboldt State University
1995-1998
Ludwig-Maximilians-Universität München
1995
In an <i>in vitro</i> model of cerebral ischemia (oxygen glucose deprivation, OGD) we investigated whether erythropoietin (EPO) plays a critical role in ischemic preconditioning. We found that EPO time and dose-dependently induced protection against OGD rat primary cortical neurons. Protection was significant at 5 min reached maximum 48 hr after application. blocked by the coapplication soluble Epo receptor (sEpoR) or antibody EpoR (anti-EpoR). Medium transfer from OGD-treated astrocytes to...
Pneumococcus is the most common and aggressive cause of bacterial meningitis induces a novel apoptosis-inducing factor–dependent (AIF–dependent) form brain cell apoptosis. Loss production two pneumococcal toxins, pneumolysin H2O2, eliminated mitochondrial damage Purified or H2O2 induced microglial neuronal apoptosis in vitro. Both toxins increases intracellular Ca2+ triggered release AIF from mitochondria. Chelating effectively blocked death. In experimental meningitis, colocalized with...
Dopamine is the predominant catecholamine in brain and functions as a neurotransmitter. also potent immune modulator. In this study, we have characterized expression of dopamine receptors on murine microglia. We found that cultured primary microglia express D1, D2, D3, D4, D5 receptors. specifically focused D2 receptor (D2R), major target antipsychotic drugs. Whereas D2Rs were strongly expressed striatal neurons vivo, did not detect any D2R resident healthy brains wild-type mice or...
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...
Using online in vivo chemiluminescence (CL), we studied for the first time continuously production of reactive oxygen species (ROS) after global cerebral ischemia and relationship ROS to CBF. In anesthetized rats equipped with a closed cranial window, CL enhancer, lucigenin (1 mM), was superfused onto brain topically. measured through window cooled photomultiplier, CBF simultaneously laser-Doppler flowmetry. Reperfusion 10 min (n = 8) led peak 188 +/- 77% (baseline 100%) within 4 min. After...
Abstract Innate immunity relies on pattern recognition receptors to detect the presence of infectious pathogens. In case Gram-positive bacteria, binding bacterial lipopeptides TLR2 is currently regarded as an important mechanism. present study, we used synthetic lipopeptide Pam3CysSK4, a selective agonist, induce meningeal inflammation in rodents. 6-h rat model, intrathecal application Pam3CysSK4 caused influx leukocytes into cerebrospinal fluid (CSF) and induced marked increase regional...
Bacterial toxins such as pneumolysin are key mediators of cytotoxicity in infections. Pneumolysin is a pore-forming toxin released by Streptococcus pneumoniae, the major cause bacterial meningitis. We found that pneumococcal factor accounts for cell death pathways induced live bacteria primary neurons. The activity essential induction mitochondrial damage and apoptosis. colocalized with membranes, altered membrane potential, caused release apoptosis-inducing death. neuronal apoptosis without...
Stroke leads to energy failure and subsequent neuronal cell loss. Creatine phosphocreatine constitute a cellular buffering transport system, dietary creatine supplementation was shown protect neurons in several models of neurodegeneration. Although has recently been found reduce infarct size after cerebral ischemia mice, the mechanisms neuroprotection remained unclear. We provide evidence for augmented blood flow (CBF) stroke creatine-treated mice using magnetic resonance imaging (MRI)-based...
Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg−1 paclitaxel (PTX), mimicking clinical conditions of dose-dense followed by pulse bromodesoxyuridine (BrdU) label dividing cells. In this model, developed memory impairments, we measured peak...
Abstract TNF-α, inducible NO synthase (iNOS), and ICAM-1 are considered to be key proteins in the inflammatory response of most tissues. We tested hypothesis that cell walls Streptococcus pneumoniae (PCW), common cause adult bacterial meningitis, induce iNOS, expression rat primary brain microvascular endothelial cultures. detected TNF-α mRNA by RT-PCR already 1 h after stimulation with PCW, while protein peaked at 4 (9.4 ± 3.6 vs 0.1 pg/μg protein). PCW induced iNOS 2 stimulation, followed...
Major barriers separating the blood from tissue compartments in body are composed of endothelial cells. Interaction bacteria with such defines course invasive infections, and meningitis has served as a model system to study cell injury. Here we report impressive ability Streptococcus pneumoniae, clinically one most important pathogens, induce 2 morphologically distinct forms programmed death (PCD) brain-derived Pneumococci major cytotoxins H2O2 pneumolysin apoptosis-like PCD independent TLR2...
Reduced infarct volume in TLR2-knockout mice compared with C57Bl/6 wild-type has recently been shown experimental stroke and confirmed this study. We now also show a significant decrease of CD11b-positive cell counts decreased neuronal death the ischemic hemispheres TLR2-deficient C57Bl/6wt 2 days after transient focal cerebral ischemia. To examine potential benefit intravascular TLR2 inhibition, were treated intraarterially TLR2-blocking anti-TLR2 antibody (clone T2.5) 45 minutes ischemia...
The metabolic state of a cell is key determinant in the decision to live and proliferate or die. Consequently, balanced energy metabolism regulation apoptosis are critical for development maintenance differentiated organisms. Hypoxia occurs physiologically during exercise pathologically vascular disease, tumorigenesis, inflammation, interfering with homeostatic metabolism. Here, we show that hypoxia-inducible factor (HIF)-1–regulated glycolytic enzyme hexokinase II (HKII) acts as molecular...
Cell wall compounds of gram-positive bacteria are capable inducing the biosynthesis proinflammatory cytokines in CNS cells a similar way as lipopolysaccharide (LPS) gram-negative does. Astrocytes, which lack CD14 LPS receptor, have also been shown to respond LPS-stimulation by increased cytokine synthesis. However, almost nothing is known about signaling steps involved this process. We therefore examined events primary cultures rat astrocytes and human astrocytoma cell line U373MG, brought...
Mendelian adult-onset leukodystrophies are a spectrum of rare inherited progressive neurodegenerative disorders affecting the white matter central nervous system. Among these, cerebral autosomal dominant and recessive arteriopathy with subcortical infarcts leukoencephalopathy, cerebroretinal vasculopathy, metachromatic leukodystrophy, hereditary diffuse leukoencephalopathy spheroids, vanishing disease present rapidly dementia as feature caused by mutations in NOTCH3, HTRA1, TREX1, ARSA,...
Astroglia and microglia, the most numerous cells in central nervous system (CNS), have been shown to produce inducible nitric oxide synthase (iNOS) tumor necrosis factor-α (TNF-α) upon stimulation with cytokines IFN-γ, IL-1β, or bacterial lipopolysaccharides (LPS). However, it is not known whether gram-positive bacteria like Streptococcus pneumoniae cause astroglial release (NO) TNF-α. S. meningitis still has a high incidence mortality spite of antibiotic therapy. Cell wall components from...
Group B Streptococcus (GBS) and pneumoniae (SP) are leading causes of bacterial meningitis in neonates children. Each pathogen produces a pore-forming cytolytic toxin, β-hemolysin/cytolysin (β-h/c) by GBS pneumolysin SP. The aim this study was to understand the role these cytotoxins, particular β-h/c, as potential neurotoxins experimental neonatal meningitis.Meningitis induced 7- 11-day-old rats intracisternal injection wild type (WT) or SP compared with isogenic β-h/c- pneumolysin-deficient...
Abstract Microglia, the resident innate immune cells of CNS, detect invading pathogens via various receptors, including TLR. Microglia are involved in a number neurodegenerative diseases which their activation may be detrimental to neurons. It is largely unknown how this potentially deleterious action can countered on cellular level. We previously found that interaction TLR2 with group B Streptococcus (GBS), most important pathogen neonatal bacterial meningitis, activates microglia turn...
Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased turnover and rigidity cytoskeletal structures have been associated with aging cell death. Gelsolin a Ca 2+ -activated actin-severing protein that widely expressed throughout adult mammalian brain. Here, we used gelsolin-deficient ( Gsn −/− ) mice as model system filament stabilization. In mice, emigration newly generated cells from subventricular zone into olfactory bulb was slowed. vitro ,...