Abstract
Cerebral palsy (CP) is the result of a static brain lesion which causes spasticity and muscle contracture. The source of the increased passive stiffness in patients is not understood and while whole muscle down to single muscle fibres have been investigated, the smallest functional unit of muscle (the sarcomere) has not been. Muscle biopsies (adductor longus and gracilis) from pediatric patients were obtained (CP n = 9 and control n = 2) and analyzed for mechanical stiffness, in-vivo sarcomere length and titin isoforms. Adductor longus muscle was the focus of this study and the results for sarcomere length showed a significant increase in length for CP (3.6 µm) compared to controls (2.6 µm). Passive stress at the same sarcomere length for CP compared to control was significantly lower in CP and the elastic modulus for the physiological range of muscle was lower in CP compared to control (98.2 kPa and 166.1 kPa, respectively). Our results show that CP muscle at its most reduced level (the myofibril) is more compliant compared to normal, which is completely opposite to what is observed at higher structural levels (single fibres, muscle fibre bundles and whole muscle). It is noteworthy that at the in vivo sarcomere length in CP, the passive forces are greater than normal, purely as a functional of these more compliant sarcomeres operating at long lengths. Titin isoforms were not different between CP and non-CP adductor longus but titin:nebulin was reduced in CP muscle, which may be due to titin loss or an over-expression of nebulin in CP muscles.
Highlights
Cerebral palsy (CP) is the most common cause of physical disability in children (Oskoui et al, 2013)
The clinical manifestations are progressive with growth (Kerr Graham and Selber, 2003) and the spastic motor type is most commonly found in children with CP (Howard et al, 2005), first manifesting with a velocity-dependent increase in muscle stiffness, and progressing to a fixed increase in muscle stiffness over time
At matched Sarcomere lengths (SLs), passive stresses and elastic moduli were much lower in CP myofibrils compared to typically developing control myofibrils
Summary
Cerebral palsy (CP) is the most common cause of physical disability in children (Oskoui et al, 2013). Previous research has shown that the sarcomere, the basic contractile unit of skeletal muscle, is overstretched in spastic muscle tissue compared to normal, and operates at long sarcomere lengths (Lieber and Fridén, 2002; Mathewson et al, 2015; Mathewson and Lieber, 2015; Smith et al, 2011). At these increased lengths, the overstretched sarcomeres would have low active force-generating capacity (Gordon et al, 1966) and high passive forces, which agrees with the clinical situation whereby muscles are tight and weak. Despite the increased sarcomere length, the muscle portion of the muscle-tendon unit has been found to be shorter in CP muscle as compared to normal (Matthiasdottir et al, 2014; Wren et al, 2010), and has been associated with the development of static contracture
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