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在帕金森病严重病变模型中,体内给予 VEGF 和 GDNF 释放的可生物降解聚合物微球。

In vivo administration of VEGF- and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson's disease.

机构信息

NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.

出版信息

Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1183-90. doi: 10.1016/j.ejpb.2013.03.034. Epub 2013 Apr 30.

DOI:10.1016/j.ejpb.2013.03.034
PMID:23639739
Abstract

In this work, the neuroregenerative potentials of microencapsulated VEGF, GDNF and their combination on a severely lesioned rat model were compared with the aim of developing a new strategy to treat advanced stages of Parkinson's disease. Both neurotrophic factors were separately encapsulated into polymeric microspheres (MSs) to obtain a continuous drug release over time. The regenerative effects of these growth factors were evaluated using a rotation behaviour test and quantified by the number of surviving TH+cells. The biological activities of encapsulated vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF) were investigated in HUVEC and PC12 cells, respectively. The treatment of 6-OHDA-lesioned rats with GDNF microspheres and with both VEGF and GDNF microspheres resulted in improved results in the rotation behaviour test. Both groups also showed higher levels of neuroregeneration/neuroreparation in the substantia nigra than the control group did. These results were confirmed by the pronounced TH+neuron recovery in the group receiving VEGF+GDNF-MS, demonstrating regenerative effects.

摘要

在这项工作中,比较了包封 VEGF、GDNF 及其组合在严重损伤的大鼠模型中的神经再生潜力,旨在开发一种新策略来治疗帕金森病的晚期。将这两种神经营养因子分别包封到聚合物微球(MS)中,以实现随时间的持续药物释放。通过旋转行为测试评估这些生长因子的再生效果,并通过存活的 TH+细胞数量进行量化。分别在 HUVEC 和 PC12 细胞中研究了包封的血管内皮生长因子(VEGF)和胶质细胞源性神经营养因子(GDNF)的生物学活性。用 GDNF 微球和 VEGF 和 GDNF 微球治疗 6-OHDA 损伤的大鼠,在旋转行为测试中取得了更好的结果。与对照组相比,这两组在黑质中的神经再生/修复水平也更高。接受 VEGF+GDNF-MS 治疗的组中 TH+神经元的明显恢复证实了再生效果。

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