Open AccessExpression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post‐ischemia in rats
Author(s) -
Cao JiaYu,
Lin Yong,
Han YanFei,
Ding ShengHao,
Fan YiLing,
Pan YaoHua,
Zhao Bing,
Guo QinHua,
Sun WenHua,
Wan JieQing,
Tong XiaoPing
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12818
Subject(s) - nerve growth factor , penumbra , ischemia , neurogenesis , medicine , brain ischemia , striatum , morris water navigation task , neuroscience , neuroprotection , pharmacology , endocrinology , psychology , hippocampus , receptor , dopamine
Summary 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.