Project description:Background: The aim of this study is to improve our understanding of the mechanisms underlying the sparing of masticatory muscles relative to limb muscles in ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factors triggering AQM, such as muscle unloading, endotoxin-induced sepsis, and systemic exposure to CS and NMBA. Results: An altered expression was notably observed in heat-shock proteins genes, sarcomeric proteins and myostatin genes were noticed. Hence, modifications in heat-shock proteins, sarcomeric proteins and myostatin genes are in sharp contrast to alterations in the limb muscles and it is postulated that elevated heat-shock proteins and decreased sarcomeric protein and myostatin genes play a protective role in the masticatory muscle relative to limb muscle in ICU patients with AQM. Conclusions: This intervention had no significant effect on masseter muscle fiber size or force-generation capacity. This is in sharp contrast to the dramatic decrease observed in specific force in limb muscle fibers from the same animals. However, significant differences were observed between the craniofacial and the limb muscle with a masseter muscle specific regulation of i) transcriptional and growth factors like RUNX1, FOXO1A, TBX1, PGC1-β and myostatin, ii) several heat shock protein genes like HSP 90, HSP 105/110 and αB-crystallin, iii) a matrix metalloproteinase inhibitor (TIMP2) and iv) oxidative stress responsive elements such as SRXN1 and SOD2. These muscle-type specific differences, the alterations in heat shock protein, sarcomeric protein and myostatin genes are forwarded as important factors underlying the sparing of masticatory muscles compared with limb muscles in critically ill ICU patients with Acute Quadriplegic Myopathy. Keywords: Treatment, immobilization, muscle function.
Project description:We recently generated a novel genetically engineered pig model displaying the fundamental biochemical, clinical and pathological hallmarks of human DMD. To get insight into the hierarchy of molecular derangements during progression of muscular dystrophy, we performed a label free proteome analysis of biceps femoris muscle samples from 2-day-old and 3-month-old DMD and WT pigs.
Project description:We used phosphoproteomic profiling of slow-twitch (soleus, SOL) and fast-twitch (biceps femoris, BF) muscle to identify differences between these muscle types.
Project description:Background: The aim of this study is to improve our understanding of the mechanisms underlying the sparing of masticatory muscles in ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factors triggering AQM, such as muscle unloading, endotoxin-induced sepsis, and systemic exposure to CS and NMBA. Results: An increased expression was notably observed in atrogin-1, cathepsins, FoxO1a, runx1 and heat-shock proteins genes. A decreased expression in some sarcomeric proteins and myostatin genes was also noticed. Hence, modifications in heat-shock proteins and myostatin genes are in sharp contrast to alterations in the limb muscles and it is postulated that elevated heat-shock proteins and decreased myostatin genes play a protective role in the masticatory muscle in ICU patients with AQM. Conclusions: We have observed a general down-regulation of muscle proteins and myostatin. Genes involved in the UPS system, cathepsins, RUNX1, TBX1, TIMP2 and transcripts of heat-shock proteins were up-regulated. However, we have neither observed a decrease in fiber CSA or force generation, suggesting that the expected atrophic changes have been countered by a protective mechanism and myostatin downregulation. Five female domestic piglets were treated with non-depolarizing neuromuscular blocking agents (NMBA), corticosteroids(CS) and sepsis. Five female piglets were untreated.
Project description:Three male 8-week-old Wistar rats were used. The peroneal nerve of the animals was transected and sutured to the biceps femoris muscle. Four weeks later, the proximal stump was sutured to the distal stump. The animals survived for 8 weeks. All experiments were performed under Ketanest (ketamine hydrochloride, Essex Pharma GmbH, Munich, Germany; 100 mg/kg) and Rompun (xylazine hydrochloride, Bayer, Leverkusen, Germany; 10 mg/kg) anesthesia. Both substances were injected intraperitoneally. RNA was extracted from the ipsilateral and contralateral tibialis anterior muscles of each animal. The gene array analysis compared the ipsilateral muscle with the contralateral muscle of each animal. Keywords: parallel sample
Project description:Three male 8-week-old Wistar rats were used. The peroneal nerve of the animals was transected and sutured to the biceps femoris muscle. Four weeks later, the proximal stump was sutured to the distal stump. The animals survived for 8 weeks. All experiments were performed under Ketanest (ketamine hydrochloride, Essex Pharma GmbH, Munich, Germany; 100 mg/kg) and Rompun (xylazine hydrochloride, Bayer, Leverkusen, Germany; 10 mg/kg) anesthesia. Both substances were injected intraperitoneally. RNA was extracted from the ipsilateral and contralateral tibialis anterior muscles of each animal. The gene array analysis compared the ipsilateral muscle with the contralateral muscle of each animal.