Muscle metabolism and mechanical efficiency in cerebral palsy

描述(申请人提供)：脑性瘫痪(CP)影响超过750,000名儿童和成人，每年新增11,000名儿童。这会对儿童的机能和耐力能力产生巨大的终生影响，导致越来越多的儿童缺乏身体活动，行动不便，需要使用轮椅等辅助设备。即使在日常生活活动的步行等次极量活动期间，能量消耗也会增加，其原因尚不清楚。肌肉代谢因子的氧化潜能、线粒体功能和机械效率的活动是能量消耗和耐力的关键。令人惊讶的是，虽然有一些与肌肉代谢相关的因素异常的证据，但还没有对这些儿童的肌肉新陈代谢进行直接测量，也不知道它们与能量消耗增加的关系。本研究的目的是明确脑性瘫痪患儿的肌肉组织代谢、机械效率和能量消耗之间的关系。我们推测，CP儿童步行时能量消耗增加，骑自行车时机械效率降低，部分原因是骨骼肌代谢受损。其次，我们假设功能能力降低的儿童机械效率较低，这可能与代谢活动减少有关。研究对象为50名4-17岁患有典型发育障碍(TD)和脑性瘫痪的儿童。第一个目标是量化患有TD和CP的儿童行走过程中肌肉氧化能力、线粒体功能和能量消耗之间的关系。我们预测，肌肉代谢活动较低的儿童在行走过程中会有更高的能量消耗，随着年龄和不同功能水平的变化，能量消耗会进一步降低。第二个补充目标将量化分级次极量运动中的机械效率，并测量其与患有CP和TD的儿童肌肉代谢的关系。我们预测，与TD儿童相比，CP儿童的机械效率和代谢功能会更低，这一点不会像TD儿童那样随着年龄的增长而变化。这项建议的结果将导致有针对性的治疗干预措施，以改善CP儿童的日常功能，特别是那些被确定为无法继续积极参与社会的风险最大的儿童。

DESCRIPTION (provided by applicant): Cerebral Palsy (CP) affects more than 750,000 children and adults, with an additional 11,000 children added every year. There are dramatic lifelong consequences on a child's functional and endurance capacity, leading to increasing physical inactivity and limited mobility necessitating the use of assistive devices such as wheelchairs. There is an increase in energy expenditure even during submaximal activities such as during walking for activities of daily living, the reasons for which are not well understood. Muscular metabolic factors of oxidative potential and mitochondrial function and mechanical efficiency of activity are critical for energy expenditure and endurance capacity. Surprisingly, while there is some evidence of abnormalities of factors related to muscle metabolism, no direct measurements of muscle metabolism have been made in these children, nor is their relationship to increased energy expenditure known. The objective of this proposal is to define the relationship between muscle tissue metabolism, mechanical efficiency and energy expenditure of walking in children with CP. We hypothesize that increased energy expenditure during walking and decreased mechanical efficiency during cycling in children with CP is in part due to impaired skeletal muscle metabolism. Secondarily, we hypothesize that mechanical efficiency will be lower in children with reduced functional capabilities and this could be correlated with reductions in metabolic activity. 50 children with Typical Development (TD) and CP between 4‑17 years of age will be recruited for this study. The first aim will quantify the relationship between muscle oxidative capacity, mitochondrial function and energy expenditure during walking in children with TD and CP. We predict that the children with lower muscle metabolic activity will have higher energy expenditure during walking, which will be further reduced with age and across functional levels. The second complementary aim will quantify mechanical efficiency during graded submaximal exercise and measure its association with muscle metabolism in children with CP and TD. We predict that the children with CP will have lower mechanical efficiency and metabolic function compared to the children with TD and this does not change with age to the same extent as in children with TD. The results of this proposal will lead to targeted therapeutic interventions for improving daily function in children with CP, in particular in those identified as being most at risk for being unable to continue active participation in society.