Long-term Fate of Denervated Skeletal Muscle After Microvascular Flap Transfer
ANNALS OF PLASTIC SURGERY
Authors: Chang, Hak; Hwang, SeungHwan; Lim, SooA; Eo, SuRak; Minn, Kyung Won; Hong, Ki Yong
Abstract
Background Muscle flap is a valuable option in soft tissue reconstruction. Denervated skeletal muscle is known to undergo degeneration. However, information regarding histological and genetic changes in muscle free flap without reinnervation over long-term follow-up remains unclear. Methods We collected flap muscles obtained during secondary exploration surgery after more than 15 years of previous muscle free flap without reinnervation. Compared with normal muscle and fat, histomorphometric and gene expression analysis of flap muscle were performed. Results During the study period, we collected 5 samples of previous muscle free flap. The mean SD postoperative duration after free flap was 18.6 +/- 4.0 years. All flap muscles were replaced with adipose tissue based on gross and histological findings. In flap muscle, the expression of gene related to muscle-specific MYH2 gene was downregulated, whereas the expression of genes related to adipose, fibroadipogenic progenitor, and blood vessel was upregulated compared with that of normal muscle. Vascular density and pattern were also similar to those in normal fat. Conclusions We demonstrated that muscle free flap without reinnervation eventually converts into adipose tissue regardless of spontaneous reinnervation during muscle regeneration. The long-term findings of the present study will be valuable for muscle flap selection and prognosis.
Atrophy, oxidative switching and ultrastructural defects in skeletal muscle of the ataxia telangiectasia mouse model
JOURNAL OF CELL SCIENCE
Authors: Tassinari, Valentina; De Gennaro, Vincenzo; La Sala, Gina; Marazziti, Daniela; Bolasco, Giulia; Aguanno, Salvatore; De Angelis, Luciana; Naro, Fabio; Pellegrini, Manuela
Abstract
Ataxia telangiectasia is a rare, multi system disease caused by ATM kinase deficiency. Atm-knockout mice recapitulate premature aging, immunodeficiency, cancer predisposition, growth retardation and motor defects, but not cerebellar neurodegeneration and ataxia. We explored whether Atm loss is responsible for skeletal muscle defects by investigating myofiber morphology, oxidative/glycolytic activity, myocyte ultrastructural architecture and neuromuscular junctions. Atm-knockout mice showed reduced muscle and fiber size. Atrophy, protein synthesis impairment and a switch from glycolytic to oxidative fibers were detected, along with an increase of in expression of slow and fast myosin types (Myh7, and Myh2 and Myh4, respectively) in tibialis anterior and solei muscles isolated from Atm-knockout mice. Transmission electron microscopy of tibialis anterior revealed misalignments of Z-lines and sarcomeres and mitochondria abnormalities that were associated with an increase in reactive oxygen species. Moreover, neuromuscular junctions appeared larger and more complex than those in Atm wild-type mice, but with preserved presynaptic terminals. In conclusion, we report for the first time that Atm-knockout mice have clear morphological skeletal muscle defects that will be relevant for the investigation of the oxidative stress response, motor alteration and the interplay with peripheral nervous system in ataxia telangiectasia.