Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury

Abstract

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (¹H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo ¹H MRS regarding skeletal muscle injury.