Protective effect of liposome-mediated GDNF gene transfer in vivo on motor neur ons following spinal cord injury in rats

Objective To investigate the effect of liposome-m ediated GDNF in vivo gene transfer on spinal cord motor neurons after spinal c ord injury in adult rats.Methods Sixtymale Sprague-Dawley rats were divided eq ually into two groups:GDNF group and GFP group.The SCI model of acute spinal cord post-erior com pression was established according to the method of Nyst rm,and then The DC-Chol liposome and recom binant plasmid pEGFP-GDNF cD N A complexes were injected into the injured spinal cord.The expres-sion of GDN F cDNA after injection was detected by RT-PCR and fluorescence mi cro scope.T he remaining motor neurons in anterior horn and the changes of cholinesterase (CHE)and acid phosphatase(ACP)activity were observed by using Nissl and enzy me histo chemistry staining.The locomo tion function of hindlimbs of rats was evaluated using inclined plane test and BBB loco motor scale.Results RT-PCRan d fluorescence observa-tion confirmed the presence of ex pression of GDNF cDN A at1week and4weeks after injection.At 1,2,4weeks after SCI,the number of active motor neurons in anterior horn in GDNF group(20.4±3.2,2 1.7±3.6,22.5±3.4)was more than that in GFP group(16.8±2 .8,17.3±2.7,18.2±3.2)(P0.05).At 1,2weeks after SCI,the mean gray value of the CHE stained spinal motoneurons in GDNF group( 74.2±25.8,98.7±31.6)was less than that in GFP group(98. 5±32.2,134.6±45.2)(P0.01),the mean gray value of ACP in GDNF group(84.5±32.6,79.5±28.4)was more than that in G FP group(61.2±24.9,52.6±19.9)(P0.01).The lo comoti ve functional scales of rats in GDNF group were high er than that in GFP group within1to4weeks after SCI (P0.05).Conclusion GDNFin vivo gene transfe r could protect motoneu rons from death and degeneration in-duced by incomplete d spinal cord injury as well as en hance locomotive function al restora tion of hindlimbs.The results suggest that li po some-medi-ated delivery of GDNF cDNA might be a practical method to treat traumatic spinal cord in jury.