Axotomy-induced changes in rabbit hindlimb nerves and the effects of chronic electrical stimulation

Abstract

Chronic electrical stimulation and extracellular recording combined with morphological examination of nerves in this study provided a detailed description of the time course and extent of fiber atrophy when the trophic influence of the target was removed by ligation of axotomized nerves and neural activity was replaced by chronic stimulation. The major findings are that decline in amplitude of compound action potentials (CAPs) and fiber diameters is rapid after axotomy and is not reversed or prevented by chronic electrical stimulation, as would be predicted if neural activity played an essential role in maintaining normal fiber caliber. Chronic stimulation had a small short-term sparing effect in the first month after axotomy but was counterproductive over long periods. Comparison of the time course of the decline in CAP amplitude and reduction of fiber diameters with described alterations in mRNA expression of neurofilament protein indicates that the early atrophy is too rapid to be accounted for by reduced synthesis and transport of neurofilaments. It is more likely to result from modification of axonal proteins after axotomy. Replacement of neural activity with stimulation may reduce the initial atrophy but, over longer periods, exacerbates the atrophy, possibly by affecting the synthesis and transport of cytoskeletal proteins. These studies show that the trophic control of nerve fiber size is mediated primarily by functional contacts with peripheral targets and that neural activity plays a relatively small role. Without functional contacts, nerve fibers decline in diameter to stable but lower values. The atrophy was exacerbated by imposing neural activity on the relatively quiescent axotomized neurons.

A dose‐dependent facilitation and inhibition of peripheral nerve regeneration by brain‐derived neurotrophic factor

“…From these studies, we conclude that high dose BDNF does not reduce numbers of fluorescently labelled motoneurons by overtly affecting their viability. Adult motoneurons rarely die after axotomy at sites distant from their cell bodies, and remain viable even after prolonged separation from the target (Gordon et al ., 1991; Vanden Noven et al ., 1993) in contrast to neonatal motoneurons which are highly susceptible to axotomy‐induced cell death (Greensmith & Vrbova, 1996). Exogenous BDNF did not counteract this survival.…”

Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size

“…Statistical significance was accepted at the 5% level (P Ͻ 0.05). Differences between distributions were analyzed using the Kolmogorov-Smirnov test to compare cumulative distribution; frequency distributions were compared using the Mann-Whitney U-test of nonparametric distribution (Fisz, 1963;Gordon et al, 1991). Student's t-test was used to compare differences between mean values of fiber diameters, axon diameters and myelin thickness with statistical significance acceptable only at the 1% level (P Ͻ 0.01).…”

Presumptive Renshaw cells contain decreased calbindin during recovery from sciatic nerve lesions.

“…Peripheral nerve lesions are known to induce several morphological (16), biochemical (20)(21)(22)(23), and physiological (17)(18)(19) changes in a-motoneurons. The alterations in a-motoneuron physiological properties seen after sciatic nerve lesions are known to be reversible upon target reinnervation (33)(34)(35) and have been ascribed primarily to the loss of functional contact with the muscular targets, since they can be reproduced by the intramuscular administration of botulinum toxin (36) and are not prevented by chronic electric stimulation (37). The major functional changes in a-motoneurons after peripheral nerve lesions include reduced action-potential amplitude, decreased after-hyperpolarization duration, decreased axonalconduction velocity (17,19), and reduction of intramedullary axon collaterals originating from the axotomized motoneurons (38).…”