Neurodegeneration und Neurogenese in organotypischen hippokampalen

Adult neurogenesis plays a role in many physiological (memory formation) and pathological (stroke, depression) processes. Increased neurogenesis in response to brain injury was recently reported and is considered a mechanism of regeneration after neuronal loss. There are evidences that numerous factors like glutamate, inflammation, and growth factors are involved in the post-insult increase of precursors proliferation and differentiation. However the mechanism of injury-induced neurogenesis is still poorly understood. In the present study early neurogenesis in vitro in rat organotypic hippocampal slice cultures (OHC) was characterized and the complex interplay between neuronal damage, microglia activation, cell proliferation, neurogenesis and the role of inflammation after oxygen-glucose deprivation (OGD) was investigated. In addition the effect of exogenous growth factors, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), brainderived neurotrophic factor (BDNF) and nerve growth factor (NGF) on proliferation and neurogenesis in OHC in the absence and presence of injury was studied. Proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, neurogenesis by BrdU-double labeling with doublecortin (DCX) or ß-III Tubulin, neuronal damage by propidium iodide uptake, microglia by OX-42 staining, pro-inflammatory cytokines by realtime RT-PCR. Massive cell proliferation was observed in the glial envelope covering the slice. Glial envelope was formed by GFAP or GFAP/Nestin positive astrocytes and activated microglia during slice cultivation. The proliferation was lower inside of the slice culture. bFGF and EGF showed mitogenic properties in our system by increasing the number of BrdU+ cells. In addition to the dentate gyrus (DG) OHC included a second neurogenic zone: the posterior periventricle (pPV), which is a part of the lateral ventricle wall. This structure lining the stratum oriens contained Nestin+ precursors. Morphological and functional differences