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Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length.

 Lucas R. Smith  ;  Ki S. Lee  ;  Samuel R.Ward  ;  Henry G. Chambers  ;  Richard L. Lieber 
 JOURNAL OF PHYSIOLOGY-LONDON, Vol.589(pt 10) : 2625-2639, 2011 
Journal Title
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Adolescent ; Biopsy ; Cerebral Palsy/complications* ; Cerebral Palsy/physiopathology ; Child ; Contracture/etiology* ; Elasticity/physiology ; Extracellular Matrix/chemistry ; Extracellular Matrix/physiology* ; Female ; Humans ; Male ; Muscle Spasticity/physiopathology ; Sarcomeres/physiology* ; Thigh/physiopathology
Cerebral palsy (CP) results from an upper motoneuron (UMN)lesion in the developing brain. Secondary to the UMNl esion,which causes spasticity, is a pathological response by muscle - namely, contracture. However, the elements within muscle that increase passive mechanical stiffness, and therefore result in contracture, are unknown. Using hamstring muscle biopsies from pediatric patients with CP (n =33) and control (n =19) patients we investigated passive mechanical properties at the protein, cellular, tissue and architectural levels to identify the elements responsible for contracture. Titin isoform, the major load-bearing protein within muscle cells, was unaltered in CP. Correspondingly, the passive mechanics of individual muscle fibres were not altered. However, CP muscle bundles, which include fibres in their constituent ECM, were stiffer than control bundles. This corresponded to an increase in collagen content of CP muscles measured by hydroxyproline assay and observed using immunohistochemistry. In vivo sarcomere length of CP muscle measured during surgery was significantly longer than that predicted for control muscle. The combination of increased tissue stiffness and increased sarcomere length interact to increase stiffness greatly of the contracture tissue in vivo. These findings provide evidence that contracture formation is not the result of stiffening at the cellular level, but stiffening of the ECM with increased collagen and an increase of in vivo sarcomere length leading to higher passive stresses.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Ki Seok(이기석)
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