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Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested., Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis., Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA., Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018., (© 2018 Wiley Periodicals, Inc.)

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (~25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated ~2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with amiR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP. [ABSTRACT FROM AUTHOR]

Due to a highly variable distribution of intramuscular collagen content within muscle, the amount collagen content itself does not relate to the actual passive muscle properties during mechanical testing as was shown in mouse hind limb muscles (Binder-Markey et al.). Keywords: muscle mechanics; extracellular matrix; connective tissue; neuromusculoskeletal interaction; adaptation; pathology; force production - transmission phenomena EN muscle mechanics extracellular matrix connective tissue neuromusculoskeletal interaction adaptation pathology force production - transmission phenomena 1 6 6 12/08/21 20211206 NES 211206 There is a growing emphasis on the importance of muscle extracellular matrix on muscular mechanics and specifically on the effects of the interaction of the extracellular matrix (ECM) and the contractile apparatus. An experimental assessment using multi-photon excitation microscopy in mouse tibialis anterior muscle surgically dissected from the tibia and surrounding muscles showed that in isometrically activated muscle the sarcomeres re-organize their lengths into a more uniform pattern over time, whereas in the passive state their length non-uniformity remained the same (Moo and Herzog). They demonstrate how a passively lengthened muscle can also have shortened parts and how an isometric contracting muscle can also have lengthened parts along the muscle fascicles. [Extracted from the article]

This commentary is on the original article by Hedberg‐Graff et al. on pages 204–211 of this issue. [ABSTRACT FROM AUTHOR]