BFGF and EGF modulate trauma-induced proliferation and neurogenesis in juvenile organotypic hippocampal slice cultures

Since postnatal and adult mammalian brains have been shown to retain an ability to generate neurons from endogenous stem cells throughout life, these cells could play a central role in regeneration after neuronal loss. Therefore, we studied cell proliferation, glio- and neurogenesis respectively after brain injury in organotypic hippocampal slice cultures using a focal trauma by transecting Schaffer collaterals in the comu ammonis (CA) 2 region mechanically. After determination of cell death using propidium iodide, neuroregenerative processes were quantitatively analyzed by various immunohistochemical techniques at different time points post injury. As this endogenous insult-induced neurogenesis is rather inefficient, we investigated if it can be enhanced by application of exogenous growth factors. Exogenous basic fibroblast growth factor (bFGF) enhanced neurrogenesis significantly in the dentate gyrus (DG) region. A neutralizing antibody against endogenous bFGF revealed a significant decrease of basal and trauma-induced proliferation. Reverse transcription polymerase chain reaction (RT-PCR) studies exhibited a downregulation of FGF messenger ribonucleic acid (mRNA) transcription after the antibody treatment. In contrast, epidermal growth factor (EGF) increased proliferation, but not neurogenesis. A combination of bFGF and EGF displayed an EGF-like effect on proliferation and no effect on neurogenesis. These results demonstrate, that in our model bFGF but not EGF sustains neurrogenesis, whereas together the two growth factors pen-nit an increased proliferation but not neurogenesis in organic hippocampal slice cultures. (c) 2004 Elsevier B.V All rights reserved.