Age differences in morphological patterns of axonal sprouting and multiple innervation of neuromuscular junctions during muscle reinnervation following nerve crush injury.

During the first 4-20 weeks after sciatic nerve crushing injury regrowing axons return to the neuromuscular junction and its reformation is in progress. During this time period age differences in patterns of axonal reinnervation from Wistar rats, with special reference to multiple axonal innervation and sprouting, was morphologically investigated using a neuronal marker (protein gene product 9.5). In young (4 months old) and aged (24 months old) animals, terminal outgrowth at the junction consisted of offshoots extending out from the junctional zone (extraterminal sprouts), and an extraterminal sprout extending to an adjacent endplate (endplate-to-endplate connections). Endplate-to-endplate connections and a nodal sprout served as partners of multiple axonal innervation. Large and complex junctions were formed by multiple innervation and elaboration of terminal branching. The most obvious changes in aged animals were as follows. (1) There were consistently more frequent numbers of extraterminal sprouting, endplate-to-endplate connections, and multiple innervation. The rates of process extension in extraterminal sprouting, however, displayed a significant drop at 4 and 8 weeks post-crush. (2) Late in reinnervation (12, 20 weeks), persistent aberrant changes in axonal reinnervation were more frequently observed, such as clumping of poorly organized nerve bundles, aggregates of multiple extensions, and poorly developed endplate-to-endplate connections, along with disorderly development of nerve terminals. Thus, age affects the reinnervating and sprouting capabilities of axons giving rise to persistent compensatory (though impaired) growth, extension, and branching in the formation of motor pathways during muscle reinnervation and endplate regeneration. The spatiotemporal relationship of these axonal changes to that of the postsynaptic receptor region is discussed.