Denervation Changes in Mammalian Striated Muscle

Abstract

The object of the experimental enquiry which forms the subject of this paper was to determine the period for which denervated mammalian striated muscle retains its essential morphological features and the manner in which these features are ultimately modified as the period of denervation increases. In order to obtain this information it was necessary to extend the period of denervation well beyond the limits which have hitherto been employed. Few of the previous enquiries devoted to a consideration of this problem have been concerned with the gross and microscopic changes occurring in a muscle which has been deprived of its nerve supply; in those which have attention has been confined to the first few months of the process, though Tower (1935) extended her observations to cover the first year of denervation.Material and Methods The experiments were performed on 36 adult specimens of the Australian opossum, Trichosurus vulpecula. The duration of denervation in the shortest experiment was nine days and in the longest 485 days. The muscles selected for examination were the flexor carpi ulnaris, flexor carpi radialis, and pronator teres. These muscles are readily identified and have well-defined attachments from which they may be rapidly and easily separated.Under chloroform aniesthesia and with aseptic technique the median and ulnar nerves were removed on the left side between the axilla and the elbow. In 27 specimens the two nerves were interrupted at the one operation, the ulnar nerve only in three, and in six the ulnar segment was removed before the median, a variable interval elapsing between the two operations. After division the nerve ends were treated in order to prevent regenerating axons from reaching the distal stump or the denervated muscles directly. At the conclusion of each experiment the distal stumps were examined histologically in order to ascertain whether or not the measures adopted had been effective. Regenerating axons had reached the distal stump of six of the severed ulnar nerves and four of the median, and these specimens were consequently discarded. In the remainder denervation had been complete and permanent.The wounds healed rapidly and by primary intention. The involved limb adopted a characteristic attitude post-* This work was assisted by a grant from the National Health and Medical Research Council of Australia. B L operatively with the forearm supinated and the hand hyp.rextended. Elbow movements were unimpaired. Flexion at the wrist could not be performed voluntarily, but the joint remained mobile so that the hand was intermittently forced into flexion by the movements of the animal in its cage. The hyperextension at the wrist was such that, though the flexores carpi muscles arise above the elbow and are relaxed by elbow flexion, these two muscles must have been almost permanently stretched as a result of the deformity, particularly the flexor carpi ulnaris which has an additional origin below the elbow. Despite the supinated position of the forelimb the pronator teres was stretch...

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

“…In small-mammal experiments in which chronic denervation is not reversed, fiber sizes are decreased 80% (for equivalent time periods). 51 We also were unable to demonstrate increased atrophy with longer denervation periods contrary to what would be expected in an analogous situation in humans. Similar observations have been made in this rodent model.…”

“…This process, referred to as denervation atrophy, involves loss of muscle mass, muscle fiber size, and contractile composition. 16,51 While research has progressed toward ways to improve nerve regeneration and to avoid or decrease the development of these muscle changes, our focus has been on strategies to optimize and augment the functional recovery of reinnervated muscles.Anabolic steroids, which have been shown to cause hypertrophy of normal muscle, delay atrophy in immobilized muscle, and to slow progression of denervation atrophy, 9,45,59 are an obvious candidate for this application. Promising preliminary data demonstrated improved muscle contraction recovery in anabolic steroid-treated rodents following the reversal of chronic denervation of hind limb muscles.…”

“…This process, referred to as denervation atrophy, involves loss of muscle mass, muscle fiber size, and contractile composition. 16,51 While research has progressed toward ways to improve nerve regeneration and to avoid or decrease the development of these muscle changes, our focus has been on strategies to optimize and augment the functional recovery of reinnervated muscles.…”

Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production

“…One potential factor may be a loss of trophic support to the muscle following denervation. Motor neurons are known to exert a trophic effect on skeletal muscle, and in the absence of neural activity, muscle mass decreases, along with a reduction in specific force, fiber diameter, and fiber number (6,73). Loss of motor neurons, breakdown of neuromuscular junctions, or inhibition of neural signaling occurs in many neuromuscular diseases, including ALS or spinal cord injury (75), spinal muscular atrophy (56), diabetic neuropathy (72), and aging (6,41,48), and each of these situations is associated with muscle atrophy.…”

The Use of Anabolic Steroids as a Strategy in Reversing Denervation Atrophy after Delayed Nerve Repair

“…Though larger motor unit sizes (each axon innervates three to five more muscle fibers than normal) can partially compensate for the lost axons in these situations, the reestablished connections are made to atrophied and compromised muscle fibers [17]. This condition of progressively irreversible loss of muscle mass, fiber size, and contractile composition is known as "denervation atrophy" [17,52].…”