Recovery from volumetric muscle loss injury: A comparison between young and aged rats

Abstract

Termed volumetric muscle loss (VML), the bulk loss of skeletal muscle tissue either through trauma or surgery overwhelms the capacity for repair, leading to the formation of non-contractile scar tissue. The myogenic potential, along with other factors that influence wound repair are known to decline with age. In order to develop effective treatment strategies for VML injuries that are effective across a broad range of patient populations, it is necessary to understand how the response to VML injury is affected by aging. Towards this end, this study was conducted to compare the response of young and aged animal groups to a lower extremity VML injury. Young (3 months, n=12) and aged (18 months, n=8) male Fischer 344 rats underwent surgical VML injury of the tibialis anterior muscle. Three months after VML injury it was found that young TA muscle was on average 16% heavier than aged muscle when no VML injury was performed and 25% heavier when comparing VML treated young and aged animals (p<0.0001, p<0.0001). Peak contractile force for both the young and aged groups was found to decrease significantly following VML injury, producing 65% and 59% of the contralateral limbs’ peak force, respectively (p<0.0001). However, there were no differences found for peak contractile force based on age, suggesting that VML affects muscle’s ability to repair, regardless of age. In this study, we used the ratio of collagen I to MyoD expression as a metric for fibrosis vs. myogenesis. Decreasing fiber cross-sectional area with advancing age (p<0.005) coupled with the ratio of collagen I to MyoD expression, which increased with age, supports the thought that regeneration is impaired in the aged population in favor of fibrosis (p=0.0241). This impairment is also exacerbated by the contribution of VML injury, where a 77-fold increase in the ratio of collagen I to MyoD was observed in the aged group (p<0.0002). The aged animal model described in this study provides a tool for investigators exploring not only the development of VML injury strategies but also the effect of aging on muscle regeneration.

New Surgical Model for Bone–Muscle Injury Reveals Age and Gender-Related Healing Patterns in the 5 Lipoxygenase (5LO) Knockout Mouse

“…To investigate the role of 5LO in the process of simultaneous bone and muscle healing, we developed a new surgical model of MSK injury in 5LOKO animals. Despite the importance of in vivo investigation for the comprehension of bone healing, previous rodent models of bone and muscle damage focus their attention exclusively on bone formation (14,74), while the majority of studies of the on MSK healing addresses skeletal muscle (23,75) or bone, but separately (24,39). In our study, we performed a moderated simultaneous bone and muscle surgical damage, with a 1-mm diameter defect in muscle and a 0.5-mm diameter defect in the subjacent bone (Figure 2A), in order to avoid further surgical complications, such as femur fracture in aged animals.…”

Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats

“…Desmin expression in the LMLR treatment group was increased, but collagen I protein expression was not obviously affected on the 7 th day, but it was remarkably reduced on the 14 th day by LMLR. High expression of desmin can stabilize the organelles in muscle fibers, maintain certain morphology of muscle fibers, and facilitate the rapid recovery of muscle cells [34], while collagen I has an opposite function in regulating muscle recovery [35]. Therefore, LMLR treatment promoted the recovery of gastrocnemius muscle injury by regulating expression of collagen I and desmin.…”

Extracellular Matrix From Decellularized Wharton’s Jelly Improves the Behavior of Cells From Degenerated Intervertebral Disc

“…The cell count percentage has been performed comparing the positive cells with all the nuclei present in the field (the number multiplied per 100). Percentage of seeded area, defined as DAPI fluorescence in all the seeded area (panoramic picture of the whole sections was made), and laminin and fibronectin mean fluorescence intensity has been calculated using Fiji 30 software as already performed elsewhere (Kim et al, 2016;Quarta et al, 2017Quarta et al, , 2018 using 8 bit image and threshold (n = 6, 10 fields per each sample). All counts were made by two blinded operators.…”