Serial sarcomere number is substantially decreased within the paretic biceps brachii in chronic hemiparetic stroke

Abstract

A muscles structure, or architecture, is indicative of its function and is plastic; changes in input to or use of the muscle alter its architecture. Stroke-induced neural deficits substantially alter both input to and usage of individual muscles. Here, we combined novel in vivo imaging methods (second harmonic generation microendoscopy, extended field-of-view ultrasound, and fat-supression MRI) to quantify functionally meaningful muscle architecture parameters in the biceps brachii of both limbs of individuals with chronic hemiparetic stroke and in age-matched, unimpaired controls. Specifically, serial sarcomere number and physiological cross-sectional area were calculated from data collected at three anatomical scales: sarcomere length, fascicle length, and muscle volume. Our data indicate that the paretic biceps brachii had ~8,500 fewer serial sarcomeres compared to the contralateral limb (p=0.0044). In the single joint posture tested, the decreased serial sarcomere number was manifested by significantly shorter fascicles (10.7cm vs 13.6cm; p<0.0001) without significant differences in sarcomere lengths (3.58m vs. 3.54m; p=0.6787) in the paretic compared to the contralateral biceps. No interlimb differences were observed in unimpaired controls, suggesting we observed muscle adaptations associated with stroke rather than natural interlimb variability. This study provides the first direct evidence of the loss of serial sarcomeres in human muscle, observed in a population with neural impairments that lead to disuse and chronically place the affected muscle at a shortened position. This adaptation is consistent with functional consequences (increased passive resistance to elbow extension) that would amplify already problematic, neurally driven motor impairments. SIGNIFICANCE STATEMENTSerial sarcomere number determines a muscles length during maximum force production and its available length range for active force generation. Skeletal muscle length adapts to functional demands; for example, animal studies demonstrate that chronically shortened muscles decrease length by losing serial sarcomeres. This phenomenon has never been demonstrated in humans. Integrating multi-scale imaging techniques, including two photon microendoscopy, an innovative advance from traditional, invasive measurement methods at the sarcomere scale, we establish that chronic impairments that place a muscle in a shortened position are associated with the loss of serial sarcomeres in humans. Understanding how muscle adapts following impairment is critical to the design of more effective clinical interventions to mitigate such adaptations and to improve function following motor impairments.