AbstractsBiology & Animal Science

Pigment epithelium-derived factor (PEDF) is a neurotrophic factor with neuroprotective, antiangiogenic, anti-inflammatory, and anti-tumorigenic effects. We aimed to show the effects of PEDF on angiogenesis and tumor growth of malignant peripheral nerve sheath tumor (MPNST) as well as on lesion volume, cell death, cell proliferation, and behavioral outcome after brain injuries (traumatic brain injury and stroke). We used the controlled cortical impact injury (CCI) rat model to study traumatic brain injury and the middle cerebral artery occlusion (MCAO) mouse model for focal cerebral ischemia. In the first study, we demonstrated for the first time that PEDF inhibited proliferation and augmented cell death in S462 MPNST cells after 48 h of treatment in culture. Following transplantation of S462 MPNST cells in athymic nude mice, PEDF reduced MPNST tumor burden mainly due to inhibition of angiogenesis. In the second study, we detected a significant increase of PEDF mRNA levels in post-CCI rat brains. In vivo, PEDF infusion showed no significant decrease in the contusion volume, whereas the number of dead cells, activated microglia, and BrdU-positive cells around the lesion was significantly decreased. In contrast, PEDF infusion significantly increased cell proliferation in the ipsilateral subventricular zone. In the third study, our model produced an ischemic injury confined solely to striatal damage in mice. We detected no reduction in infarct size and cell death in PEDF- vs. cerebrospinal fluid-infused MCAO mice. Behavioral outcome and cell proliferation did not differ between the groups. Whereas PEDF showed a specific positive effect after traumatic brain injury in rats, we were not able to observe the same effect after striatal ischemia in the MCAO mouse model. However, we cannot exclude that PEDF might work under different conditions in stroke. Therefore, further studies will elucidate the effect of PEDF treatment on cell proliferation and outcome in moderate to severe ischemic injury in the brain. Due to its inhibitory effects on the growth of human MPNST, PEDF seems to be promising for future therapeutic purposes against MPNST. Der Pigment epithelium-derived factor (PEDF) ist ein neurotropher Faktor, der Gehirnzellen schützt, die Bildung neuer Gefäßstrukturen und die Entstehung von Tumoren verhindert sowie entzündungshemmend wirkt. Unser Ziel war es, die Auswirkungen von PEDF auf die Gefäßbildung und das Tumorwachstum bei malignen peripheren Nervenscheidentumor (MPNST) sowie auf das Läsionsvolumen, Zelltod, Zellteilung und Verhalten bei Hirnschädigungen (Schädelhirntrauma und Schlaganfall) zu zeigen. Schädelhirntrauma wurde experimentell durch kontrollierte kortikale Kontusion (CCI) in der Ratte herbeigeführt und der Schlaganfall wurde mittels Mausmodell des Verschluss der mittleren Hirnarterie (MCAO) untersucht. In der ersten Studie zeigten wir erstmals, dass sich kultivierte S462 MPNST Zellen, die 48 Stunden lang mit PEDF behandelt wurden, weniger stark teilten und stärker abstarben. Nach Transplantation…