Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat.
Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the β-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried β-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered β-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded β-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the β-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat.
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Yong
Y
Lin
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Jie-qing
JQ
Wan
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Guo-yi
GY
Gao
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Yao-hua
YH
Pan
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Sheng-hao
SH
Ding
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Yi-ling
YL
Fan
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China.
Yong
Y
Wang
Department of Neurological Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, PR China. Electronic address: jiyaojiang@126.com.
Ji-yao
JY
Jiang
D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D003071:Cognition; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics*; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
D020932:Nerve Growth Factor
Gene; Hippocampus; Nerve growth factor; Pseudo lentivirus; Traumatic brain injury