Artikel
Intraventricular infusion of PEDF causes proliferation of neural stem cells in the subventricular zone following experimental brain injury
Intraventrikuläre PEDF-Infusion verursacht Proliferation von neuralen Stammzellen in der Subventrikularzone nach experimentellem Hirntrauma
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Autoren
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E.M. Bründl
- Neurochirurgische Universitätsklinik, Klinikum der Universität Regensburg, Regensburg
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A.-L. Pina
- Neurochirurgische Universitätsklinik, Klinikum der Universität Regensburg, Regensburg
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E.-M. Störr
- Neurochirurgische Universitätsklinik, Klinikum der Universität Regensburg, Regensburg
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M. A. Proescholdt
- Neurochirurgische Universitätsklinik, Klinikum der Universität Regensburg, Regensburg
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A. Brawanski
- Neurochirurgische Universitätsklinik, Klinikum der Universität Regensburg, Regensburg
| Veröffentlicht: | 30. Mai 2008 |
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Gliederung
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Objective: Head injury is a major cause of morbidity and mortality worldwide. Unfavourable outcome i.e. death or vegetative state amounts to 34.5% of all patients with severe head injury. The brain has the capacity for self repair through proliferation of endogenous progenitor cells, provided the molecular micomileu is adequate. Pigment Epithelium-Derived Factor (PEDF) is a potent antiangiogenic and tumor-differentiating factor that can also protect and differentiate neurons. In this study we wanted to investigate the effects of PEDF on neural stem cells (NSCs) of the subventricular zone (SVZ) and the dentate gyrus (DG) in animals subjected to an experimental brain injury.
Methods: 30 rats received a controlled cortical impact injury, 5 animals were sacrificed and analyzed without trauma or treatment as sham control. The treatment control group (n=9) received the impact injury but no treatment. The remaining animals were infused intraventricularly either with PEDF 5 µg/ml (n=7) or PEDF 10 µg/ml (n=8) over a time period of 7 days using a miniosmotic pump. Control animals (n=6) received carrier infusion only. To analyze DNA synthesis, animals were injected with BrdU (50 mg/Kg bogyweight). After 8 days, the animals were sacrificed, and the brains were harvested for histologic analysis. The extent of lesion was investigated by cresyl violet staining, the analysis of stem cell proliferation was performed using immunohistochemical staining for double cortin (Dcx) and GFAP; inflammatory reactions and cell division were investigated by staining for ED-1and anti-BrdU respectively.
Results: The extent of lesion was almost identical in all treatment groups. The inflammatory reponse was not significantly different in the treatment groups. BrdU labeling was significantly enhanced in the SVZ upon treatment with PEDF in a dose dependent fashion (p=0.002). GFAP/BrdU double labeling revealed a marked increase of GFAP positive, actively deviding cells.
Conclusions: Our data suggest that PEDF infusion causes proliferation of NSCs in the SVZ. This may ultimately contribute to enhanced neurogenesis after brain injury.
