4‐Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice

Abstract

Introduction We recently demonstrated the beneficial effects of 4‐aminopyridine (4‐AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4‐AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. Methods Mice were assigned to sciatic nerve crush injury and no‐injury groups and were followed for 3, 7, and 14 days with/without 4‐AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. Results In addition to improving in vivo function, 4‐AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy‐related genes and increased expression of proliferating stem cells. Discussion These findings provide new insights into the potential therapeutic benefits of 4‐AP against nerve injury‐induced muscle atrophy and dysfunction. Muscle Nerve 60: 192–201, 2019

Synchrotron radiation imaging analysis of neural damage in mouse soleus muscle

“…Injury to the sciatic nerve can trigger muscle fatigue, aging, atrophy, and lower-limb dysfunction [4][5][6][7][8][9][10][11] . Among the muscles dominated by the sciatic nerve, the soleus muscles exhibit significant regenerative capacity to promote functional recovery [8][9][10][11] . Furthermore, when muscle atrophy is prominent, less myogenin is expressed to increase elasticity against muscle damage 12 .…”

“…Studies investigating these phenomena usually conduct histochemical analyses using animal experiments 8,9,11 . Microscopic imaging and micro-CT imaging have also been employed to observe changes (such as injury or recovery) observed from the condition of mouse soleus muscle.…”

Functional recovery with histomorphometric analysis of nerves and muscles after combination treatment with erythropoietin and dexamethasone in acute peripheral nerve injury

“…Because our primary goal was to show functional recovery with combination pharmacotherapy, we chose to use an established murine model of sciatic nerve crushing injury [3,5,9,11,24]. Evaluating the functional response of animals with PNI to drug treatments is critical in evaluating their potential for actual clinical use in human.…”

“…PNI can also occur iatrogenically during routine orthopedic surgical procedures such as compression of the nerve during fixation with screws or wires, direct insult to the nerve from soft tissue dissection, and stretching of the nerve due to soft tissue retraction. Despite the availability of modern diagnostic tools and recent microsurgical advances, patients with PNI do not attain full functional recovery [3]. Because axonal regeneration and growth support of Schwann cells diminish with increasing time and distance from the injury site, the timely regeneration of axons are required in order to regain satisfactory function [4].…”

A novel nerve transection and repair method in mice: histomorphometric analysis of nerves, blood vessels, and muscles with functional recovery

“…After functional analysis on post-surgery day 28, tibialis anterior (TA) muscles of contralateral and injured hind limbs were harvested from surrounding tissues and weighed. H&E staining and histomorphometric analysis of TA muscles were performed as described previously 43 . Briefly, muscles were washed in chilled PBS and immediately transferred to 30% sucrose and kept at 4 °C until tissue sank to bottom.…”