Yasuhara Takao, Shingo Tetsuro, Muraoka Kenichiro, wen Ji Yuan, Kameda Masahiro, Takeuchi Akira, Yano Akimasa, Nishio Shinsaku, Matsui Toshihiro, Miyoshi Yasuyuki, Hamada Hirofumi, Date Isao
Department of Neurological Surgery, Okayama University Graduate School of Medicine Dentistry, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
Brain Res. 2005 Mar 15;1038(1):1-10. doi: 10.1016/j.brainres.2004.12.055.
Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects on dopaminergic (DA) neurons. In this study, we investigated whether the effects of VEGF were dose-dependent or not. First, VEGF was shown to be neuroprotective on 6-hydroxydopamine (6-OHDA)-treated murine DA neurons in vitro, although the 1 ng/ml of VEGF displayed more neuroprotective effects than 100 ng/ml. Furthermore, using 2 sizes of capsules (small/large) with different secreting quantities, 6-OHDA-treated rats receiving the small capsule filled with VEGF-secreting cells (BHK-VEGF) into the striatum showed a significant decrease in amphetamine-induced rotational behavior in number and a significant preservation of TH-positive fibers compared to those receiving the large BHK-VEGF capsule as well as those receiving BHK-Control capsule. Rats receiving the large BHK-VEGF capsule showed much more glial proliferation, angiogenesis, and brain edema around the capsule than those with the small one. High-dose administration of VEGF might cause poor circulation related to brain edema, although low-dose administration of VEGF displays neuroprotective effects on DA neurons. Our results demonstrate the importance of administration dose of VEGF, suggesting that low-dose administration of VEGF might be desirable for Parkinson's disease.
血管内皮生长因子（VEGF）先前已被证明对多巴胺能（DA）神经元具有神经保护作用。在本研究中，我们调查了VEGF的作用是否呈剂量依赖性。首先，VEGF在体外对6-羟基多巴胺（6-OHDA）处理的小鼠DA神经元具有神经保护作用，尽管1 ng/ml的VEGF比100 ng/ml表现出更强的神经保护作用。此外，使用两种不同分泌量的胶囊（小/大），将填充有分泌VEGF细胞（BHK-VEGF）的小胶囊植入6-OHDA处理的大鼠纹状体后，与接受大的BHK-VEGF胶囊以及接受BHK对照胶囊的大鼠相比，其苯丙胺诱导的旋转行为次数显著减少，TH阳性纤维得到显著保留。接受大的BHK-VEGF胶囊的大鼠在胶囊周围出现了比接受小胶囊的大鼠更多的胶质细胞增殖、血管生成和脑水肿。高剂量的VEGF可能会导致与脑水肿相关的血液循环不良，而低剂量的VEGF对DA神经元具有神经保护作用。我们的结果证明了VEGF给药剂量的重要性，表明低剂量给药VEGF可能对帕金森病有益。
