Macrophages, muscle stem cells, and repair; immunohistochemical characteristics in muscle growth impairments in children with cerebral palsy

Children with cerebral palsy (CP) have muscle growth impairments (muscle contractures), altered walking patterns and show markers of inflammation. During muscle repair, macrophages coordinate with muscle stem cells-satellite cells (MuSCs), which have previously been shown to be altered in abundance and function in children with CP. We investigated whether <i>1</i>) macrophage populations in contractured muscles of children with CP are similar to typically developing (TD) children with a chronic anterior cruciate ligament (ACL)-tear and <i>2</i>) macrophages, capillaries, MuSC, myonuclei, centrally nucleated fibers were associated with each other, indicative of repair. Thirty-six subjects participated in this study (CP: 11.2 ± 0.7 yr, 18 M/12F, TD: 13.5 ± 0.8 yr, 3 M/3 F). Muscle biopsies were obtained during surgical correction for muscle contractures-adductors/gastrocnemius (CPCon), or vastus lateralis (TD-ACL and CP NonCon). Muscle cross sections were immunohistochemically labeled for total, anti-inflammatory (M2) macrophages, capillaries, myofiber boundaries, whereas MuSC abundance, activation, and proliferation information were used from a prior study. Macrophage subpopulations in CPCon were similar to TD-ACL muscles. Within CPCon, there were positive associations between total, M1 macrophages, and MuSC content (<i>r</i> = 0.54, <i>r</i> = 0.70, <i>P</i> < 0.05, respectively), but not in the CP NonCon muscles. Centrally nucleated fibers, myonuclear abundance, and MuSC content were also positively associated with each other only in the CPCon muscles (<i>r</i> = 0.65, <i>r</i> = 0.46, <i>r</i> = 0.66, <i>P</i> < 0.05, respectively). In TD-ACL injured muscles, similar associations were seen between macrophages and MuSC, central nucleation and myonuclear abundance. Collectively, our data suggest that contractured muscles in children with CP may be in a state of repair, similar to ACL-injured TD children.<b>NEW & NOTEWORTHY</b> Muscle growth impairments seen as muscle contractures are common in children with cerebral palsy. Here we show these muscles appear to have altered macrophage populations, which are similar to joint injury-induced muscle inflammation in typically developing children. Only within contractured muscles, macrophage content, muscle stem cell abundance, capillary density and fiber characteristics are positively associated with each other, indicative of repair, similar to that seen in joint injury-induced muscle inflammation.