Effects of pathway and neuronal aging on the specificity of motor axon regeneration

Youth is a strong predictor of functional recovery after peripheral nerve r epair, while adulthood is commonly associated with poor outcome. Identifica tion of the factors responsible for this difference could form the basis fo r strategies to improve regeneration in adults. Preferential reinnervation of motor pathways by motor axons (PMR) occurs strongly in young rats, but i s often absent in older animals, and thus parallels the overall trend for s uperior results in young individuals. These experiments evaluate the indivi dual contributions of peripheral nerve age and motoneuron age to the declin e in regeneration specificity (PMR) which accompanies the aging process. Th e femoral nerves of young and old Lewis rats were removed as inverted "Y" g rafts from the femoral trunk proximally to the terminal muscle and cutaneou s branches distally. These grafts were transferred from (1) old to young, ( 2) young to old, (3) old to old, and (4) young to young bilaterally in 10 i ndividuals per group. After 8 weeks of regeneration, reinnervation of cutan eous and muscle branches was assessed by dual labeling with HRP and Fluoro- Gold. Motor neuron regeneration was random in old to old (mean muscle branc h (M) = 159, mean cutaneous branch (C) = 168), but PMR was seen when young pathways were used in old animals (M = 163, C = 116). PMR was vigorous when either type of graft was used in young animals (young graft, M = 218, C = 134; old graft, M = 204, C = 127). In this model, motoneuron age appears to be the primary determinant of specificity. However, the pathway also makes significant contributions, as shown by the ability of young pathways to ge nerate specificity in old animals. Manipulation of graft Schwann cell behav ior might therefore be an appropriate strategy to improve outcome in older individuals. (C) 2001 Academic Press.