Disuse muscle atrophy exacerbates motor neuronal degeneration caudal to the site of spinal cord injury

Abstract

Spinal cord injury is often followed by disuse muscle atrophy. The effect of disuse muscle atrophy on motor neurons below the level of spinal cord lesions is not fully understood. We produced spinal contusions in the mid-thoracic segment (Th7/8) of rats. To promote disuse muscle atrophy, their hind limbs were immobilized. Alpha-motor neurons in L4/5 at 3 weeks postinjury showed signs of degeneration associated with disuse muscle atrophy. Muscle atrophy alone did not produce a significant α-motor neuronal degeneration. Our results demonstrate that disuse muscle atrophy within the context of spinal cord injury exacerbates motor neuronal degeneration in caudal regions remote from the injury.

Depletion of Glial Cell Line-Derived Neurotrophic Factor by Disuse Muscle Atrophy Exacerbates the Degeneration of Alpha Motor Neurons in Caudal Regions Remote from the Spinal Cord Injury

“…We have previously reported that disuse muscle atrophy within the context of spinal cord injury exacerbates not only MN degeneration in caudal regions remote from the injury but also the decrease in GDNF protein level in paralyzed muscle [11]. In this study, disuse muscle atrophy was associated with a significant decrease in GDNF protein levels in the L4/5 spinal cord.…”

“…Although normal muscle is a source of TFs for spinal MNs, there is a considerable decrease in TF levels in atrophic muscles, in part due to elevated levels of ubiquitin ligases and decreased protein synthesis [6]- [8]. It has been reported that limb immobilization produces atrophic muscles [6] [9]- [11]. On the other hand, training increases TFs including GDNF in skeletal muscle [12] [13].…”

Abnormal feeding behaviour in spinalised rats is mediated by hypothalamus: Restorative effect of exposure to extremely low frequency magnetic field

“…The BWT was significantly decreased in our SCI rats-that is in line with the existing literature. 51 Loss of BWT can be attributed to reduction in food and WI besides marked osteoporosis, 44,62,63 sublesional disuse wasting of muscles 64,65 and other metabolic effects 66 in transection model of SCI. Primeaux et al 51 reported a decrease in BWT after complete transection of spinal cord at T3 in female rats, which was maintained until week 18.…”

What Is Being Trained? How Divergent Forms of Plasticity Compete To Shape Locomotor Recovery after Spinal Cord Injury

“…Although musculoskeletal plasticity can occur in mild-to-moderate SCI and can be facilitated by ambulatory training, the long-term limb immobilization just after severe SCI prevents plasticity from contributing to recovery of muscles. [76][77][78][79][80] Whereas much attention has been given to the effects of SCI-induced limb immobilization on musculoskeletal plasticity, 81 a number of preclinical studies have shown that maladaptive spinal plasticity produced by inappropriate afferent input can play a pivotal role in undermining future locomotor recovery, developing hyper-reflexia, spasticity, and intractable pain. 82,83 Preclinical work by Caudle and colleagues has shown that in a wheelchair model of acute limb immobilization after SCI, immobilized rats show significantly less locomotor recovery if compared with non-immobilized rats as control.…”