Mitochondrial respiration and characteristics of skeletal muscles in children with cerebral palsy
Sudarshan Dayanidhi, Guadalupe Meza, Ryan E. Kahn, Timothy Krater, Addison Barber, Tasos Karakostas, Craig J. Finlayson, Ishan Roy, Neeraj M. Patel, Jill E. Larson, Vineeta T. SwaroopAbstract
Aim
To assess mitochondrial respiration and characteristics across muscles in children with cerebral palsy (CP) and to evaluate whether they were different from injury‐induced atrophy in children with typical development.
Method
Thirty‐two children with CP (mean age 11 years 5 months, standard deviation 7 months; 21 males, 11 females; 16 classified in Gross Motor Function Classification System levels I–III), and 14 typically developing children with anterior cruciate ligament (ACL) injury (mean age 14 years 10 months, standard deviation 7 months; eight males, six females) participated in this cross‐sectional study. Muscle biopsies were obtained from the vastus in ACL‐injured children with typical development during ACL repair, from adductor, from gastrocnemius during surgical release of contractures, or from vastus lateralis during derotational osteotomy in children with CP. We assessed whether mitochondrial respiration, characteristics, and capillary properties using immunohistochemistry in permeabilized muscle fiber bundles were different in children with CP compared with injury‐induced atrophy in children with typical development.
Results
Pediatric ACL injuries negatively affect mitochondrial properties in vastus muscles, which have lower function and content than vastus muscles in those with CP. In children with CP, the mitochondrial properties of gastrocnemius muscles appear to be different from those in typically developing children with injury‐induced atrophic processes with higher function and content, while adductor muscles have similar mitochondrial function but higher content as the children with typical development. In a subset of ambulatory children, clinical characteristics of contractures and gait were associated with muscle mitochondrial respiration.
Interpretation
Mitochondrial properties in muscle contractures in children with CP are different from injury‐induced atrophy. Potential therapies to improve mitochondrial function either through exercise or other therapeutics might lead to improved muscle metabolic health.