Severe burn increased skeletal muscle loss in mdx mutant mice

Abstract

Background-Severe burn causes muscle mass loss and atrophy. The balance between muscle cell death and growth maintains tissue homeostasis. We hypothesize that pre-existing cellular structural defects will exacerbate skeletal muscle mass loss after burn. Using a Duchenne muscular dystrophy (mdx) mutant mouse, we investigated whether severe burn caused more damage in skeletal muscle with pre-existing muscle disease.Methods-The mdx mice and wild type mice received 25% total body surface area (TBSA) scald burn. Gastrocnemius, tibialis anterior, and gluteus muscles were obtained at day 1 and 3 after burn. Gastrocnemius muscle function was measured on day 3. Animals without burn served as controls.Results-Wet tissue weight significantly decreased in tibialis anterior and gluteus in both mdx and wild type mice after burn (p<0.05). The ratio of muscle-to-body weight decreased in mdx mutant mice (p<0.05) but not wild type. Isometric force was significantly lower in mdx gastrocnemius and this difference persisted after burn (p<0.05). Caspase-3 activity increased significantly after burn in both groups, while HMGB1 expression was higher in burn mdx mice (p<0.05). Proliferating cell nuclear antigen (PCNA) decreased significantly in mdx mice (p<0.05).Myogenic markers pax7, myoD and myogenin increased after burn in both groups, and were higher in mdx mice (p<0.05).Conclusion-More muscle loss occurred in response to severe burn in mdx mutant mice. Cell turnover in mdx mice after burn is differed from wild type. Although markers of myogenic activation are elevated in mdx mutant mice, the underlying muscle pathophysiology is less tolerant of traumatic injury.

Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats

“…Plasma HMGB1 levels were increased in patients with burn on > 10% TBSA at the time of hospitalization, and the secreted HMGB1 levels correlated with burn size and poor survival outcomes in burn patients 18 . HMGB1 level in gastrocnemius lateral muscle of rats exposed to burn on 30% TBSA (vs. sham burn) was increased by 164.80%, similar to what was observed in our previous study of burn mouse model 37 and treatment with HMGB1 Ab improved the muscle mass in burn rats. These findings provide evidence for the pathological role of burn induced systemic increase in HMGB1 in muscle loss and imply that HMGB1 neutralization will prevent the muscle mass loss and muscle wasting after burn.…”

ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury

“…Previous studies demonstrated that the pathophysiological response to burn injury alters the balance between skeletal muscle protein anabolism and catabolism [ 10 ]. This results in immediate loss of skeletal muscle mass [ 11 – 13 ]. Interestingly, it was shown that burn injury results in atrophy and myogenesis stimulation in muscle due to a host systemic response, although myogenesis does not compensate for burn-induced cell death [ 14 , 15 ].…”

Skeletal muscle transcriptome is affected by age in severely burned mice

“…Gastrocnemius tissue contains mixed slow-and fast- myofiber types, and its anatomic location is far away from burn wound site in mouse trunk. We and others analyzed the gastrocnemius tissue to represent the muscle response to systemic influence in mouse and rat models 38 , 39 . Gastrocnemius tissues (~ 25 mg) were processed for total RNA extraction using Qiagen RNeasy Mini Kit (Germantown, MD).…”