Artikel
In vivo effects of Pigment epithelium derived factor on injured brain
Wirkung von PEDF beim Hirntrauma
Suche in Medline nach
Autoren
Veröffentlicht: | 8. Mai 2006 |
---|
Gliederung
Text
Objective: Pigment epithelium-derived factor (PEDF) is a potent antiangiogenic and tumor-differentiating factor that can also protect and differentiate neurons. The neurotrophic effects of PEDF on brain cells has been demonstrated mainly by in vitro experiments that showed the ability of the protein to support the survival of neurons in the presence of various neurotoxic stimuli and, in some cases, to induce neuronal differentiation. In this study we report the in vivo effects that PEDF exerts on neurogenesis, apoptosis and proliferation of microglia cells after brain injury.
Methods: Adult male rats were subjected to unilateral cortical impact injury. In the same animals PEDF and/or aCSF (vehicle) were administered into the lateral ventricle as well as they received intraperitoneal injections of Bromo-deoxy-Uridine (BrdU) over a period of 7 days. The brain tissues from these animals were prepared for histological analysis. Detection of BrdU (for proliferating cells), single stranded DNA (for apoptotic cells) and ED1 antigen (for activated microglia), were performed using immunocytochemical methods. The number of labelled cells into the lesioned and neurogenic (subventricular zone, SVZ, and the subgranular layer of the dentate gyrus of the hippocampus, DG) zones was measured using a computer-assisted stereology system.
Results: Our preliminary results show that infusion of PEDF is associated with a reduced area of the lesion. With increasing PEDF concentrations, proliferating cells into the SVZ appeared to decrease in number. When comparing the different experimental groups, no changes in proliferating cells could be detected in the DG. At the lesioned area, both, the number of apoptotic cells as well as of microglia cells appeared to be diminished by the presence of PEDF.
Conclusions: Our results indicate that in vivo PEDF may be a multifunctional neuroprotective agent, influencing neurogenesis, apoptosis and inflammatory processes. Further experimental work has to be performed in order to analyse the mechanisms underlying its neuronal activities.
We thank E.M. Stoerr for excellent technical assistance.