Chapter 26: Age-related differences in the reinnervation after peripheral nerve injury

Numerous and extensive functional, structural, and biochemical changes characterize intact aged peripheral nervous system. Functional recovery after peripheral nerve injury depends on survival of injured neurons and functional reinnervation of target tissue by regeneration of injured axons and collateral sprouting of uninjured (intact) adjacent axons. The rate of axonal regeneration becomes slower and its extent (density and number of regenerating axons) decreases in aged animals. Aging also impairs terminal sprouting of regenerated axons and collateral sprouting of intact adjacent axons, thus further limiting target reinnervation and its functional recovery. Decreased survival of aged noninjured and injured neurons, limited intrinsic growth potential of neuron, alteration in its responsiveness to stimulatory or inhibitory environmental factors, and changes in the peripheral neural pathways and target tissues are possible reasons for impaired reinnervation after peripheral nerve injury in old age. The review of present data suggests that this impairment is mostly due to the age-related changes in the peripheral neural pathways and target tissues, and not due to the limited intrinsic growth capacity of neurons or their reduced responsiveness to trophic factors. Age-related alterations in the soluble target derived neurotrophic factors, like nerve growth factor, and nonsoluble extracellular matrix components of neural pathways, like laminin, might be important in this respect.