Effects of LIF dose and laminin plus fibronectin on axotomized sciatic nerves

Leukemia inhibitory factor (LIF), a cytokine which has neurotrophic and myo trophic activities, has been shown to enhance nerve regeneration and conseq uent return of muscle function in the entubulation model of sciatic nerve r epair. Fibronectin (FN) and laminin (LN) are two extracellular matrix (ECM) components that, when combined, promote axon growth in the entubulation mo del. The aim of this study was to determine the optimal LIF dose and the ef ficacy of FN plus LN administered either alone or simultaneously with the o ptimal LIF dose. We found that at 12 weeks following nerve repair, a single 10 ng LIF dose produced the largest medial gastrocnemius (MG) muscle mass (P < 0.0001) and maximum force contraction (P < 0.001). The diameter of the axons in the FN plus LN group were significantly greater than for saline ( P < 0.001) and the LIF dose groups (P < 0.01), When 10 ng LIF was combined with FN plus LN, the MG muscle mass was significantly greater than the opti mal LIF dose (P < 0.05), suggesting an additive effect. Our findings suppor t the view that combinations of factors, which perhaps act on complementary mechanisms for nerve regeneration, will be required to maximally potentiat e nerve regeneration and return of muscle function after nerve injury. (C) 2000 John Wiley & Sons, Inc.