Abstract
We here suggest that pigment epithelium-derived factor (PEDF) does not have an effect on lesion size, behavioral outcome, cell proliferation, or cell death after striatal ischemia in the mouse. PEDF is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. It influences self-renewal of neural stem cells and proliferation of microglia. We investigated whether intraventricular infusion of PEDF reduces infarct size and cell death, ameliorates behavioral outcome, and influences cell proliferation in the one-hour middle cerebral artery occlusion (MCAO) mouse model of focal cerebral ischemia. C57Bl6/N mice were implanted with PEDF or artificial cerebrospinal fluid (control) osmotic pumps and subjected to 60-minute MCAO 48 hours after pump implantation. They received daily BrdU injections for 7 days after MCAO in order to investigate cell proliferation. Infarct volumes were determined 24 hours after reperfusion using magnetic resonance imaging. We removed the pumps on day 5 and performed behavioral testing between day 7 and 21. Immunohistochemical staining was performed to determine the effect of PEDF on cell proliferation and cell death. Our model produced an ischemic injury confined solely to striatal damage. We detected no reduction in infarct sizes and cell death in PEDF- vs. CSF-infused MCAO mice. Behavioral outcome and cell proliferation did not differ between the groups. However, we cannot exclude that PEDF might work under different conditions in stroke. Further studies will elucidate the effect of PEDF treatment on cell proliferation and behavioral outcome in moderate to severe ischemic injury in the brain.
Highlights
Stroke is one of the leading causes of death and disability in the Western societies
The objective of this study was to investigate whether pigment epithelium-derived factor (PEDF) can ameliorate behavioral outcome as well as cell death and influences cell proliferation upon focal cerebral ischemia
We demonstrate here that in an ischemic lesion confined to the striatum, PEDF does not exert its previously described protective effects, and has no effect on lesion size, behavioral outcome, cell proliferation, or cell death
Summary
Stroke is one of the leading causes of death and disability in the Western societies. The only effective therapy is thrombolysis with recombinant tissue plasminogen activator. Neurotrophic factors, including pigment epithelium-derived factor (PEDF), are of increasing interest for therapy. They prevent initialization of cell death while promoting differentiation of neuronal progenitor cells [2]. Its known effects include neurotrophism, neuroprotection, antitumorigenesis, and antiangiogenesis [3]. PEDF is produced in most mammalian tissues, including the brain [4,5,6]. It was found in striatum [7], cerebellum [8], hippocampus and hypothalamus [9] as well as cerebral cortex [9,10,11]
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