Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys
Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys
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DOI：
10.1016/j.nbd.2006.04.014
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发表时间：
2006-08-01
影响因子：
6.1
通讯作者：
Kordower, Jeffrey H.
中科院分区：
文献类型：
--
作者：
Emerich, Dwaine F.;Thanos, Christopher G.;Kordower, Jeffrey H.
亨廷顿氏病（HD）是纹状体神经元变性的结果。脉络膜丛（CP）细胞分泌神经营养因子，CP移植对HD大鼠模型具有神经保护作用。为了确定在灵长类动物中是否可以获得类似的神经保护作用，将猪CP包被在海藻酸盐胶囊中。PCR证实CP细胞表达转甲状腺素，免疫细胞化学显示典型的ZO-1和微管蛋白染色。在体外，CP条件培养基提高了血清缺失神经元的存活率，并保留了神经元突起的数量和长度。将装载cp的胶囊植入食蟹灵长类尾状核和壳核，1周后进行喹啉酸（QA）损伤。对照组猴子得到的是空胶囊和QA。通过neun阳性神经元的体视计数（减少8%，对照组为43%）和纹状体体积（减少10%，对照组为40%）显示，脉络膜丛移植显著保护纹状体神经元。这些数据表明CP移植可能有助于预防HD患者的神经元变性。(c) 2006爱思唯尔公司版权所有。
Huntington's disease (HD) results from degeneration of striatal neurons. Choroid plexus (CP) cells secrete neurotrophic factors, and CP transplants are neuroprotective in rat models of HD. To determine if similar neuroprotective effects could be obtained in primates, porcine CP was encapsulated in alginate capsules. PCR confirmed that the CP cells expressed transthyretin and immunocytochemistry demonstrated typical ZO-1 and tubulin staining. In vitro, CP conditioned media enhanced the survival and preserved neurite number and length on serum deprived neurons. Cynomolgus primates were transplanted with CP-loaded capsules into the caudate and putamen followed by quinolinic acid (QA) lesions 1 week later. Control monkeys received empty capsules plus QA. Choroid plexus transplants significantly protected striatal neurons as revealed by stereological counts of NeuN-positive neurons (8% loss vs. 43% in controls) and striatum volume (10% decrease vs. 40% in controls). These data indicate that CP transplants might be useful for preventing the degeneration of neurons in HD. (c) 2006 Elsevier Inc. All rights reserved.