Department of Neurobiology, Physiology, & Behavior, University of California Davis, Davis, CA, USA.
Department of Orthopaedic Surgery, Shriners Children's Northern California, Sacramento, CA, USA.
J Physiol. 2024 Jul;602(14):3489-3504. doi: 10.1113/JP285988. Epub 2024 Jun 20.
Cerebral palsy (CP) describes some upper motoneuron disorders due to non-progressive disturbances occurring in the developing brain that cause progressive changes to muscle. While longer sarcomeres increase muscle stiffness in patients with CP compared to typically developing (TD) patients, changes in extracellular matrix (ECM) architecture can increase stiffness. Our goal was to investigate how changes in muscle and ECM architecture impact muscle stiffness, gait and joint function in CP. Gracilis and adductor longus biopsies were collected from children with CP undergoing tendon lengthening surgery for hamstring and hip adduction contractures, respectively. Gracilis biopsies were collected from TD patients undergoing anterior cruciate ligament reconstruction surgery with hamstring autograft. Muscle mechanical testing, two-photon imaging and hydroxyproline assay were performed on biopsies. Corresponding data were compared to radiographic hip displacement in CP adductors (CPA), gait kinematics in CP hamstrings (CPH), and joint range of motion in CPA and CPH. We found at matched sarcomere lengths muscle stiffness and collagen architecture were similar between TD and CP hamstrings. However, CPH stiffness (R = 0.1973), collagen content (R = 0.5099) and cross-linking (R = 0.3233) were correlated to decreased knee range of motion. Additionally, we observed collagen fibres within the muscle ECM increase alignment during muscular stretching. These data demonstrate that while ECM architecture is similar between TD and CP hamstrings, collagen fibres biomechanics are sensitive to muscle strain and may be altered at longer in vivo sarcomere lengths in CP muscle. Future studies could evaluate the impact of ECM architecture on TD and CP muscle stiffness across in vivo operating ranges. KEY POINTS: At matched sarcomere lengths, gracilis muscle mechanics and collagen architecture are similar in TD patients and patients with CP. In both TD and CP muscles, collagen fibres dynamically increase their alignment during muscle stretching. Aspects of muscle mechanics and collagen architecture are predictive of in vivo knee joint motion and radiographic hip displacement in patients with CP. Longer sarcomere lengths in CP muscle in vivo may alter collagen architecture and biomechanics to drive deficits in joint mobility and gait function.
脑性瘫痪（CP）描述了一些由于在发育中的大脑中发生的非进行性障碍而导致的上运动神经元疾病，这些障碍导致肌肉进行性变化。虽然与正常发育（TD）患者相比，CP 患者的肌节变长会增加肌肉僵硬，但细胞外基质（ECM）结构的变化也会增加僵硬。我们的目标是研究肌肉和 ECM 结构的变化如何影响 CP 患者的肌肉僵硬、步态和关节功能。分别从接受跟腱延长术治疗腘绳肌和髋关节内收挛缩的 CP 患者以及接受前交叉韧带重建术伴腘绳肌自体移植的 TD 患者中采集了内收长肌和长收肌活检。对活检标本进行肌肉力学测试、双光子成像和羟脯氨酸测定。将相应数据与 CP 内收肌的髋关节放射位移（CPA）、CP 腘绳肌的步态运动学（CPH）以及 CPA 和 CPH 的关节活动范围进行比较。我们发现，在匹配的肌节长度下，TD 和 CP 腘绳肌的肌肉僵硬和胶原结构相似。然而，CPH 僵硬（R=0.1973）、胶原含量（R=0.5099）和交联（R=0.3233）与膝关节活动范围减小相关。此外，我们观察到肌肉 ECM 内的胶原纤维在肌肉拉伸过程中增加了排列。这些数据表明，虽然 TD 和 CP 腘绳肌的 ECM 结构相似，但胶原纤维的生物力学对肌肉应变敏感，在 CP 肌肉的更长体内肌节长度下可能会发生改变。未来的研究可以评估 ECM 结构对 TD 和 CP 肌肉僵硬在体内工作范围内的影响。关键要点：在匹配的肌节长度下，TD 患者和 CP 患者的内收长肌力学和胶原结构相似。在 TD 和 CP 肌肉中，胶原纤维在肌肉拉伸过程中动态增加其排列。肌肉力学和胶原结构的某些方面可预测 CP 患者的体内膝关节运动和髋关节放射位移。CP 肌肉在体内的较长肌节长度可能会改变胶原结构和生物力学，从而导致关节活动度和步态功能的缺陷。
