Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats
Autor: | Yan-Fei Han, Yong Lin, Wen-Hua Sun, Yao-hua Pan, Bing Zhao, Jieqing Wan, Yi-ling Fan, Shenghao Ding, Jia-Yu Cao, Xiao-Ping Tong, Qin-Hua Guo |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Microinjections Genetic enhancement Green Fluorescent Proteins Ischemia Morris water navigation task Apoptosis Striatum Pharmacology Statistics Nonparametric Rats Sprague-Dawley 03 medical and health sciences GAP-43 Protein 0302 clinical medicine Transduction Genetic Physiology (medical) Nerve Growth Factor In Situ Nick-End Labeling medicine Animals Pharmacology (medical) Maze Learning Neurons TUNEL assay business.industry Penumbra Lentivirus Neurogenesis Infarction Middle Cerebral Artery Recovery of Function Original Articles medicine.disease Rats Disease Models Animal Psychiatry and Mental health 030104 developmental biology Nerve growth factor Gene Expression Regulation nervous system Phosphopyruvate Hydratase Cognition Disorders business 030217 neurology & neurosurgery |
Zdroj: | CNS Neuroscience & Therapeutics. 24:508-518 |
ISSN: | 1755-5930 |
DOI: | 10.1111/cns.12818 |
Popis: | 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 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. Results 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. Conclusion 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. |
Databáze: | OpenAIRE |
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