Juvenile and adult rat neuromuscular junctions: Density, distribution, and morphology

Abstract

Anatomical and physiological differences in neuromuscular junctions (NMJs) between juvenile and adult muscle may partially explain the variability in clinical results following chemodenervation with botulinum toxin or nerve repair in children and adults. We evaluated NMJ density, distribution, and morphometry in biceps brachii and gastrocnemius muscles from juvenile and adult rats. Motor endplates were stained with Karnovsky-Roots methods, and NMJ density (number/gram muscle tissue) was determined. The NMJ morphometry was quantitated with alpha-bungarotoxin labeling using confocal microscopy. Juvenile rats had a greater NMJ density in both muscles compared with adult rats. Juveniles and adult rats had a similar NMJ distribution in both muscles. In juvenile muscles NMJs occupied approximately 50% of the surface area and 70% of the length, width, circumference, and gutter depth compared with adult muscles. Our study demonstrates that although NMJs are smaller, juvenile muscles have a higher NMJ density than do adult muscles with similar distributions. If these age-dependent differences in NMJ density are obtained in humans, they may account, at least in part, for the better recovery that occurs in children than adults after nerve repair and also suggest that the dosage of botulinum toxin (units per kg) for chemodenervation may need to be increased in juveniles.

Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice

“…19 Initial observations also suggest that the mouse gastrocnemius has approximately a fifth of the neuromuscular junctions (data unpublished) of the rat gastrocnemius. 32 Identifying the lowest dose capable of producing the desired inhibition in the smallest injection volume is critical for minimizing patient risks associated with BoNTA permeating neighboring muscles and the development of antibody resistance to BoNTA. 8,33 Antibody formation to BoNTA can result from repeated injections administered in a short time period, injections of high number of toxin units from overestimating the U/kg body weight ratio necessary to inhibit response, and the cumulative dose administered over multiple treatments.…”

The Concept of «Key Muscles» and the Early Onset of Botulinum Therapy in Spastic Forms of Cerebral Palsy

“…С этой точки зрения, раннее введение БТА в мышцы детей с ДЦП первых лет жизни может влиять на процесс созревания и распределения, а также на мор-фологию концевых пластинок. Экспериментальные рабо-ты на крысах показали анатомические и физиологиче-ские отличия нервно-мышечных соединений у молодых и взрослых особей, что может отчасти объяснять раз-личия в клинической эффективности использования инъек ций БТА в разных возрастных группах людей [71]. Учитывая имеющиеся данные о слабости и структурных изменениях паретичных мышц при ДЦП, дополнительное повреждение концевых пластинок при раннем введении БТА было бы крайне нежелательным [72].…”

Botulinum toxin and its orthopaedic applications

“…Children receive a lower dose than adults although in an animal model, Ma et al 17 noted that while the neuromuscular junctions are smaller in juveniles their density within muscle is higher than that in the adult. If this is representative of age-dependent differences, then relatively higher doses in children may be appropriate, similar to the pattern of use with anaesthetic neuromuscular blocking agents.…”