Molecular mechanisms by which targeted muscle reinnervation improves the microenvironment of spinal cord motor neurons and target muscles

Abstract

Targeted muscle reinnervation is a clinically valuable nerve transfers technology used to reconstruct the information sources reconstruct the motor nerve information sources lost because of nerve injury. This study aimed to investigate the effects and underlying molecular mechanisms of hind limb TMR on motor neurons and target muscles in rats after tibial nerve transection (TNT). Immunohistochemistry was performed to detect acetylcholinesterase expression in the target muscles and myelin basic protein, neuregulin-1 (NRG1), and ErbB2 expression in the tibial nerve of rats. Masson's trichrome staining was performed to observe fibrillar collagen expression in the target muscles. Western blot analysis was used to detect the protein expression of NRG1 and its receptor, ErbB2, in the target muscles. TMR significantly enhanced NRG1, ErbB2, and myelin basic protein expression in nerve fibers compared with those in the TNT group and exerted a protective effect on the maintenance of a large number of nerve fibers and myelin sheath thickness. The above results indicated that TMR can regulate NRG1 and ErbB2 expression in residual nerve fibers and protect the integrity of the myelin sheath, thus improving the functional status of the target muscles, which is beneficial for restoring hind limb motor function after TNT.

Keywords: Motor neuron; Nerve injury; Neuregulin-1; Target muscle; Targeted muscle reinnervation.