Résumé :
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The TS is an expiratory muscle that is passively stretched with each inspiration and concentrically activated with each expiration. The degree of passive stretch of TS muscle fibers depends upon the location of the fiber within the muscle, with caudal fibers stretched up to 10% more than cephalad fibers (DeTroyer et al., J. Physiol. (Lond.) 513.3, 915-925, 1998). Cross sections of adult nondystrophic TS indicate roughly uniform fiber density in the caudal, middle, and cephalad thirds of the muscle and fiber diameters that increase significantly in the cephalad to caudal direction. In comparison to age-matched nondystrophic mice, the density of muscle fibers in mdx TS muscles at 1 to 2 years of age was significantly reduced in the middle and cephalad regions of the TS muscle, and the cross-sectional diameter significantly reduced in all 3 regions. The total working diameter and working cross sectional area of mdx TS muscle was also significantly reduced relative to nondystrophic values. Increased centronucleation was observed in all 3 regions of the mdx TS muscle. Transmission electron micrographs from mdx TS indicate substantial Z line streaming, sarcomere disorganization, and numerous hypercontracted areas where dense myofilamentous material was observed adjacent to empty sarcoplasm containing numerous mitochondria. Long term treatment of mature adult mdx mice with pyrrolidine dithiocarbamate (PDTC; 50 mg/kg, intraperitoneal) produced a significant increase in fiber diameter in the middle TS and reduced centronucleation throughout the TS. Daily treatment with N-acetylcysteine (NAC; 100 mg/kg, ip) for a period of 3.5 months also significantly increased the fiber diameter and fiber cross-sectional area in the cephalad region of the mdx TS. These results provide evidence supporting the utility of the mdx TS preparation in assessing the morphological benefits of a variety of potential treatments for Duchenne and related muscular dystrophies. (Supported by AFM, Charley’s Fund, Strategic Research Grant from ATSU)
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