Synergistic effects of NGF, CNTF and GDNF on functional recovery following sciatic nerve injury in rats

ABSTRACTPurposeTo investigate the synergistic effects of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and glia cell line-derived neurotrophic factor (GDNF) on survival and growth of sensory neurons and motoneurons, as well as on the functional recovery following sciatic nerve injury in rats.MethodsExperimental rats and neurons were randomized into 8 groups: NGF group, CNTF group, GDNF group, NGF+CNTF group, CNTF+GDNF group, NGF+GDNF group, NGF+CNTF+GDNF group and control group. Each group received local intramuscular injection of indicated NTFs according to the treatment protocol. The sciatic nerve function index (SFI), nerve conduction velocity and wet weight recovery rate of gastrocnemius muscle were tested to evaluate the functional recovery in vivo. A 2 (presence or absence of NGF) × 2 (presence or absence of CNTF) × 2 (presence or absence of GDNF) analysis of variance (ANOVA) was used to examine the main effects and interactions among NGF, CNTF and GDNF, and one-way ANOVA was calculated for multiple comparison.ResultsNGF and GDNF acted significantly on the survival of sensory neuron and motoneuron, respectively. CNTF was a dominant factor promoting cell body development, and GDNF had the most powerful effect on neurite outgrowth and elongation of sensory neurons and motoneurons. Combined administration of the three factors resulted in optimal functional recovery following sciatic nerve injury in rats.ConclusionsIt is demonstrated that differential and complementary biological effects of various neurotrophic factors contribute to synergistic promotion of nervous function recovery.