Effects of GDNF gene-activated matrix on neuron protection after sciatic nerve injury in rats / 重庆医科大学学报

ABSTRACT

Objective:To evaluate the effects of glial cell line-derived neurotrophic factor(GDNF) gene-activated matrix(GAM) in protection of neurons after sciatic nerve injury.Methods:The peripheral nerve extracellular matrix was harvested by chemical extraction.GDNF GAM was comprised of the extracellular matrix and plasmids encoding GDNF.Sixty adult Wistar rats were randomly divided into three groupsgroup A(GDNF GAM conduits,n=20),group B(ECM conduits,n=20),group C(autografts,n=20).Lumbar enlargement was processed for Nissl staining,immunohistochemistry and RT-PCR for GDNF or iNOS and fluorescence observation.Fluorescence observation was used to confirm the expressing of GDNF in the spinal cord.Motoneurons(MN) of lesioned(L) and normal(N) sides were counted,and MN survival ratio(MSR=L/N) was calculated.Results:GDNF DNA can be retained in GAM,promoting transgene expressing in axotomized neurons in spinal cord for 12 weeks.In GAM group,the expression of GDNF mRNA was maintained for 12 weeks while the number of iNOS positive cells was decreased in comparison with ECM group.GAM grafts obviously increased the survival rate of motor neurons than that of ECM grafts(78.04%?3.50% vs 56.09%?1.89%) at 12 weeks postaxotomy.Conclusion:These results suggest that(1) GDNF GAM increases the GDNF mRNA and the amount of Nissl positive cells in the lumber enlargement;(2) GDNF GAM protects MN through a mechanism in relation to iNOS.