title: Transcutaneous carbon dioxide application accelerates muscle injury repair in rat models.
abstract: Skeletal muscle injuries are commonly observed in sports and traumatology medicine. Previously, we demonstrated that transcutaneous application of carbon dioxide (CO2) to lower limbs increased the number of muscle mitochondria and promoted muscle endurance. Therefore, we aimed to investigate whether transcutaneous CO2application could enhance recovery from muscle injury.
  
  
  
  Tibialis anterior muscle damage was induced in 27 Sprague Dawley rats via intramuscular injection of bupivacaine. After muscle injury, rats were randomly assigned to transcutaneous CO2-treated or -untreated groups. From each group, three rats were sacrificed at weeks one, two, four and six. At each time point, histology and immunofluorescence analyses were performed, and changes in muscle weight, muscle weight/body weight ratio, muscle fibre circumference, gene expression levels and capillary density were measured.
  
  
  
  Injured muscle fibres were completely repaired at week six in the CO2-treated group but only partially repaired in the untreated group. The repair of basement and plasma membranes did not differ significantly between groups. However, expression levels of genes and proteins related to muscle protein synthesis were significantly higher in the CO2-treated group and significantly more capillaries four weeks after injury.
  
  
  
  Transcutaneous CO2application can accelerate recovery after muscle injury in rats.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Akahane
authors.affiliation: Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. yossie@med.kobe-u.ac.jp.
authors.forename: Yoshitada
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Division of Rehabilitation Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.|NeoChemir Inc., Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueha
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hanako
authors.initials: H
authors.lastname: Nishimoto
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niikura
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002245:Carbon Dioxide
keywords: Capillary density; Muscle injury; Transcutaneous CO2