Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat

Abstract 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.