Abstract:

Objective
To observe the neuoprotective effect of  lentiviral vector expressing and secreting neuroprotective peptide (NAP) on closed head injury in mice via nose-brain pathway and provide theoretical basis for  treatment of  neurodegeneration diseases by lentiviral vector secreting NAP. Methods 54 adult male  Kunming mice were divided into four groups：control group(n=10),closed head jnjury group (CHI,n=20),rLent/NT4-NAP group(rLent,n=20), and rLent/GFP group  (GFP,n=4).The  mortality,NSS and brain edema in various groups were observed.The pathological changes in brain injury region of various  groups stained by HE were observed.The expressions of GFP in nasal epithelium olfactory nerve and brain tissue in GF
P group were detected under laser confocal microscope.Results The  mortality of mice in rLent group (15%) was significantly lower than that in CHI group（55%）. The NSS in  rLent group  were lower than those in CHI groups at 1,3,5 and 7 d after brain injury（P<0.01）.The percentage of H2O in rLent group  was  lower than that in CHI group at 24 h after brain injury（P<0.01）.HE staining result showed that the  pathological changes in rLent group were  fewer  than those in  CHI group.There was significant GFP in the nasal epithelium,but no fluorescenc
e in olfactory nerve and brain tissue.Conclusion The recombinant rLent/NT4-NAP could efficietnly infect nasal epithelium in vivo.NAP provides significant neuroprotective effect from the complex array of injuries elicited by head trauma.The recombinant rLent/GFP could only infect nasal epithelium,but not go through blood-brain barrier (BBB) to central nervous system (CNS).

Key words: neuroprotective peptide NAP;lentiviral vector;gene therapy;closed head injury