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The role and influence of pigment epithelium-derived factor (PEDF) on peripheral nerve tumor, brain trauma and stroke
Terzi, Menderes Yusuf

HaupttitelThe role and influence of pigment epithelium-derived factor (PEDF) on peripheral nerve tumor, brain trauma and stroke
TitelvarianteDie Rolle und der Einfluss des Pigment epithelium-derived factor (PEDF) am peripheren Nerventumor, Hirn-Trauma und Schlaganfall
AutorTerzi, Menderes Yusuf
Geburtsort: Kastamonu, Türkei
GutachterN.N.
weitere GutachterN.N.
Freie SchlagwörterPEDF; neuroprotection; peripheral nerve tumor; brain trauma; MCAO
DDC610 Medizin und Gesundheit
ZusammenfassungPigment 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.
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Seitenzahl34
Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2015
Dokumententyp/-SammlungenDissertation
Medientyp/FormatText
SpracheEnglisch
Rechte Nutzungsbedingungen
Tag der Disputation30.05.2015
Erstellt am15.05.2015 - 10:46:53
Letzte Änderung15.05.2015 - 10:49:19
 
Statische URLhttp://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000098863
URNurn:nbn:de:kobv:188-fudissthesis000000098863-0
Zugriffsstatistik
E-Mail-Adressemenderes-yusuf.terzi@charite.de