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色素上皮衍生因子对创伤性脑损伤的影响。

Effects of pigment epithelium-derived factor on traumatic brain injury.

作者信息

Terzi Menderes Yusuf, Casalis Pablo, Lang Veronika, Zille Marietta, Bründl Elisabeth, Störr Eva-Maria, Brawanski Alexander, Vajkoczy Peter, Thomale Ulrich, Piña Ana Luisa

机构信息

Neurosurgery Department and Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Experimental Neurology Department, Charité - Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Restor Neurol Neurosci. 2015;33(1):81-93. doi: 10.3233/RNN-140417.

Abstract

PURPOSE

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, anti-inflammatory, neurotrophic and neurogenic properties. The effect of PEDF on traumatic brain injury (TBI) has not been explored. In this study, we aimed to show the in vivo effects of PEDF on lesion volume, cell death and cell proliferation after TBI.

METHODS

Rats were subjected to controlled cortical impact injury (CCII). PEDF mRNA brain levels were measured by RT-PCR. The lesion volume, cell proliferation, cell death and microglia activation were assessed in the brains of lesioned animals with intraventricular alzet infusion of PEDF or aCSF, and intraperitoneal injections of BrdU.

RESULTS

We detected a significant increase of PEDF mRNA levels after TBI. PEDF intraventricular infusion showed no significant effect on the contusion volume, whereas the number of dead cells, activated microglia, BrdU-positive cells around the lesion were significantly decreased. In contrast, PEDF application increased cell proliferation in the ipsilateral subventricular zone. No effect was found on cell proliferation in the dentate gyrus.

CONCLUSION

The present work indicates that PEDF acts as a multifunctional agent after TBI influencing cell death, inflammation and cell proliferation.

摘要

目的

色素上皮衍生因子(PEDF)是一种具有抗血管生成、抗炎、神经营养和神经发生特性的多功能蛋白质。PEDF对创伤性脑损伤(TBI)的影响尚未得到研究。在本研究中,我们旨在展示PEDF对TBI后损伤体积、细胞死亡和细胞增殖的体内作用。

方法

对大鼠进行控制性皮质撞击损伤(CCII)。通过RT-PCR测量PEDF mRNA的脑内水平。对脑室注射PEDF或人工脑脊液(aCSF)并腹腔注射溴脱氧尿苷(BrdU)的损伤动物脑内的损伤体积、细胞增殖、细胞死亡和小胶质细胞活化情况进行评估。

结果

我们检测到TBI后PEDF mRNA水平显著升高。脑室内注入PEDF对挫伤体积无显著影响,而损伤周围的死亡细胞数量、活化小胶质细胞数量、BrdU阳性细胞数量显著减少。相比之下,应用PEDF可增加同侧脑室下区的细胞增殖。对齿状回的细胞增殖未发现影响。

结论

目前的研究表明,PEDF在TBI后作为一种多功能因子发挥作用,影响细胞死亡、炎症和细胞增殖。

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