Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats
Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats
复制标题
假型慢病毒携带的神经生长因子的表达可改善大鼠缺血后的神经元存活和认知功能恢复。
DOI：
10.1111/cns.12818
复制
发表时间：
2018-06-01
影响因子：
5.5
通讯作者：
Tong, Xiao-Ping
中科院分区：
文献类型：
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作者：
Cao, Jia-Yu;Lin, Yong;Tong, Xiao-Ping
目的：神经生长因子（NGF）在动物脑损伤模型和人类缺血性疾病中具有预防神经元损伤和促进功能恢复的作用。我们的目的是研究神经生长因子基因治疗在缺血性中风中的潜在治疗效果，并在缺血大鼠模型中评估细胞和认知水平的功能恢复。在将假病毒递送的β-NGF微量注射到建立的大鼠缺血性中风模型（tMCAO）中后，我们用TUNEL标记和细胞增殖标记物Ki 67染色来评估纹状体缺血核心区和半暗区的神经细胞凋亡和神经发生。此外，我们使用行为功能测试，Morris水迷宫性能，以评估在体内的认知功能恢复，并提出一个潜在的潜在mechanism.Results：我们发现，假病毒介导的β-NGF基因到脑内的交付诱导高表达在纹状体的梗死核心区缺血后大鼠。缺血后纹状体梗死核心区的β-NGF过表达不仅通过减少细胞凋亡和增加细胞增殖来改善神经元存活，而且还通过上调tMCAO大鼠缺血模型中GAP-43蛋白表达来挽救认知功能障碍。这项研究表明，潜在的β-利用假慢病毒进行神经生长因子基因治疗缺血性脑血管病的研究，为神经生长因子基因治疗缺血性脑血管病的应用提供了新的思路。
Aims: Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model.Methods: After microinjection of pseudolentivirus-delivered beta-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism.Results: We found that pseudolentivirus-mediated delivery of beta-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The beta-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia.Conclusion: This study demonstrates a potential beta-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.