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
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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