Trauma associated muscle wasting

The mechanisms regulating immobilisation and trauma associated muscle wasting

Principal Investigator: Dr Matthew Brook

The project was awarded £13,300 from the University of Nottingham National Rehabilitation Centre and Faculty of Medicine and Health Sciences strategic funds via an open call held in March 2022.

The following activities were completed during the period April to July 2022:

Activities Completed

Injury and surgical repair induce significant muscle trauma and inflammation which are associated with impaired physical function and increased morbidity. These negative effects of injury and trauma are in part due to associated losses of muscle mass and strength and disruption of energy metabolism.

Similarly, immobilisation in the absence of trauma induces muscle mass and strength losses and dysregulation of energy metabolism, but whether common pathways regulate these phenotypic traits is unknown. An increased understanding of the molecular mechanisms of surgical trauma and immobilisation-induced muscle dysfunction could lead to more targeted and effective strategies to offset muscle decline and optimise rehabilitation.

This study used existing RNA derived from muscle biopsies collected from the gastrocnemius of ankle fracture patients. Muscle biopsies were collected from the injured and uninjured leg at time of surgery and two weeks into recovery. In addition, muscle biopsies were collected from age and gender matched healthy controls who underwent two weeks of unilateral cast immobilisation, with muscle biopsies collected at baseline and after immobilisation. Collectively these samples as such represent: i) immobilisation alone, and ii) immobilisation + inflammation, with appropriate control limbs, thus permitting delineation of the mechanisms of traumatic injury and/or immobilisation on muscle biology.

To investigate these mechanisms, we will perform RNA transcriptomic analyses of these samples using high throughput RNASeq technologies to identify gene expression associated with immobilisation and the interaction of immobilisation with traumatic inflammatory. This will identify core gene networks implicated in immobilisation and trauma induced muscle wasting and metabolic dysregulation.

Outcomes

The RNA has been successfully extracted from the muscle samples. The samples have undergone library construction and RNA transcriptomic sequencing with data analysis currently ongoing.

Future Plans

Upon completion of this work, we will have generated a list of candidate gene and biological networks implicated in the pathological sequelae associated with immobilisation and trauma induced muscle wasting. The mechanisms uncovered through this work will generate potential for future follow-on funding.