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Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.

CNS neuroscience & therapeutics (2018-02-07)
Jia-Yu Cao, Yong Lin, Yan-Fei Han, Sheng-Hao Ding, Yi-Ling Fan, Yao-Hua Pan, Bing Zhao, Qin-Hua Guo, Wen-Hua Sun, Jie-Qing Wan, Xiao-Ping Tong
ABSTRACT

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. After microinjection of pseudolentivirus-delivered β-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. We found that pseudolentivirus-mediated delivery of β-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The β-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. This study demonstrates a potential β-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.

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Monoclonal Anti-S100B antibody produced in mouse, Prestige Antibodies® Powered by Atlas Antibodies, clone CL2720, purified immunoglobulin, buffered aqueous glycerol solution
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Fluoromount Aqueous Mounting Medium, for use with fluorescent dye-stained tissues