Zille Marietta, Riabinska Arina, Terzi Menderes Yusuf, Balkaya Mustafa, Prinz Vincent, Schmerl Bettina, Nieminen-Kelhä Melina, Endres Matthias, Vajkoczy Peter, Pina Ana Luisa
Department of Experimental Neurology, Center for Stroke Research Berlin, Charite - Universitaetsmedizin Berlin, Berlin, Germany.
Department of Neurosurgery, Charite - Universitaetsmedizin Berlin, Berlin, Germany.
PLoS One. 2014 Dec 3;9(12):e114595. doi: 10.1371/journal.pone.0114595. eCollection 2014.
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.
我们在此表明，色素上皮衍生因子（PEDF）对小鼠纹状体缺血后的损伤大小、行为结果、细胞增殖或细胞死亡没有影响。PEDF是一种具有神经保护、抗血管生成和抗通透性作用的神经营养因子。它影响神经干细胞的自我更新和小胶质细胞的增殖。我们研究了在局灶性脑缺血的一小时大脑中动脉闭塞（MCAO）小鼠模型中，脑室内注入PEDF是否能减小梗死体积和细胞死亡、改善行为结果并影响细胞增殖。将C57Bl6/N小鼠植入PEDF或人工脑脊液（对照）渗透泵，并在泵植入后48小时进行60分钟的MCAO。MCAO后，它们每天接受7天的BrdU注射，以研究细胞增殖。再灌注24小时后，使用磁共振成像确定梗死体积。我们在第5天取出泵，并在第7天至第21天之间进行行为测试。进行免疫组织化学染色以确定PEDF对细胞增殖和细胞死亡的影响。我们的模型产生的缺血性损伤仅局限于纹状体损伤。我们发现在注入PEDF与注入脑脊液的MCAO小鼠中，梗死体积和细胞死亡没有减少。两组之间的行为结果和细胞增殖没有差异。然而，我们不能排除PEDF在中风的不同条件下可能起作用。进一步的研究将阐明PEDF治疗对脑中度至重度缺血性损伤中细胞增殖和行为结果的影响。
