„Forum neurologicum” der Deutschen Gesellschaft für Neurologie
Erwin Volles2000, Aktuelle Neurologie
Sign up for access to the world's latest research
Abstract
Die Stiftung wurde von Klaus Felgenhauer (1933-2002) gegründet. Er hinterließ der Stiftung sein Vermögen mit dem Ziel, junge Neurowissenschaftler zu fördern. Gefördert werden Assistenten neurologischer und psychiatrischer Kliniken, die in der Regel nicht älter als 30 Jahre sein sollen. Auch junge Wissenschaftler aus theoretischen Instituten oder Kliniker aus Grenzgebieten der Neurologie und Psychiatrie können gefördert werden, wenn sie Projekte mit klinischer Relevanz verfolgen. Die Förderung wird pro Einzelfall bis zu einer Höhe von 3000 € gewährt, bevorzugt für kurze Studienaufenthalte in einem angesehenen Labor des In-und Auslandes. Auch die Teilnahme an wissenschaftlich hochkarätigen Tagungen im Ausland kann gefördert werden. Voraussetzung hierfür ist die Präsentation eigener Forschungsergebnisse. Die Anträge sind mit einer kurzen Projektbeschreibung, einer Kostenschätzung und einem kurzen Lebenslauf einschließlich wissenschaftlichen Werdegangs in 5-facher Ausfertigung bis zum 30.6.2011 einzusenden an Herrn Prof. Dr. Volles, Gerhart-Hauptmann-Str. 28, in 38723 Seesen. Berichte von geförderten Projekten Adam, Nina et al.: Evangelisches Krankenhaus Göttingen, Geriatrisches Zentrum. The viral TLR3 agonist poly I : C stimulates phagocytosis and intracellular killing of Escherichia coli by microglial cells. European Congress of Clinical Microbiology an Infectious Diseases, Wien, 10.-13.04.2010. Objectives: Escherichia coli Kl meningitis is associated with a high rate of mortality and long-term sequelae despite antimicrobial therapy, especially in pediatric patients. Microglial cells, the resident phagocytes in the CNS, express Toll-like receptors (TLR) that mediate the innate immune response upon recognition of invading pathogens. Polyinosine-polycytidylic acid [poly(I : C)] is a TLR3 agonist structurally similar to viral doublestranded RNA. Here, we show that a viral TLR3 agonist can stimulate microglial cells and increase their phagocytic activity and intracellular killing of E. coli Kl, a pathogenic encapsulated bacterial strain. Methods: Primary cultures of murine microglia were exposed to poly(I : C) at 0.1 or 10 mg / l for 24 h. A control group of unstimulated cells was included in all experiments. After stimulation, supematants were collected and stored at-80°C until measurement of cyto-/ chemokine levels. Microglial cultures were co-incubated with live E. coli K1 for phagocytosis and intracellular killing assays at a ratio of 100 bacteria per cell. Phagocytosis was left to proceed for 30 and 90 min at 37°C. For phagocytosis inhibition studies, cytochalasin D (CD) was used at 10 microM. For intracellular killing assays, cells were incubated with bacteria for 90 min. After bacterial exposure, microglial cultures were washed and cultured in medium containing gentamiein (200 mg / l). At various time points, cells were washed and lysed with distilled water. Viable intracellular bacteria were enumerated by quantitative plating of serial 10-fold dilutions. ANOVA (followed by Bonferroniʼs multiple comparisons test) was performed to analyse differences between groups (n ≥ 11); p < 0.05 was considered statistically significant. Results: The supernatants of unstimulated cells were devoid of measurable amounts of cyto-/ chemokines. Unstimulated microglia ingested bacteria at a low rate. Poly(I : C) stimulated murine microglial cultures in a dose-dependent manner to secrete TNF-alpha and CXCLI and increase their ability to phagocytose (p < 0.05 after 30 min, p < 0.01 after 90 min) and kill intracellular E. coli Kl. CD blocked the bacterial uptake by ≥ 90 %. Conclusions: Stimulation of microglia with a viral agonist of the TLR system such as poly(I : C) could increase the resistance of the brain to bacterial infections. This may be a promising approach to protect the brain of septicemic patients from meningitis, cerebritis and brain abscess.
