Influence of Eccentric Exercise on Muscle and Joint Health After ACL Injury

离心运动对 ACL 损伤后肌肉和关节健康的影响

基本信息

批准号：
10045602
负责人：
Lindsey K Lepley
金额：
$ 12.69万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10045602
关键词：
Address Affect American Animal Model Anterior Cruciate Ligament Area Attenuated Belief Biological Biological Markers Biomechanics C-reactive protein Cartilage Clinical Clinical Trials Connecticut Coupled Data Degenerative polyarthritis Development Effectiveness Engineering Evidence based treatment Exercise Fiber Foundational Skills Frequencies Future Gait Goals Health Hindlimb Human In Situ In Vitro Inflammation Inflammatory Inflammatory Response Injury Interleukin-1 beta Interleukin-6 Joints Knee Knee joint Lead Length Link Literature Long-Evans Rats Masks Measures Mechanical Stress Mentored Research Scientist Development Award Modeling Monitor Morphology Motion Muscle Muscle Weakness Musculoskeletal Operative Surgical Procedures Orthopedics Outcome Patients Phase Physiological Positioning Attribute Procedures Proteoglycan Protocols documentation Rattus Recovery Rehabilitation therapy Reporting Reproducibility Research Research Personnel Rodent Rodent Model Role Scanning Scientist Serum Severities Stretching Surgeon System TNF gene Testing Thick Time Training Training Programs Universities anterior cruciate ligament injury anterior cruciate ligament reconstruction bone career career development cartilage degradation clinical translation clinically translatable cost disability evidence base exercise prescription experience functional disability high risk population improved in vivo joint injury limb injury mathematical model microCT mode of exercise muscle strength novel prevent primary outcome programs protective effect quadriceps muscle rehabilitation strategy relating to nervous system response response to injury skill acquisition skills standard of care strength training substantia spongiosa systematic review

项目摘要

PROJECT SUMMARY The purpose of this K01 Mentored Research Scientist Development Award is to promote Dr. Lindsey Lepley’s independent research program by training under Dr. David Goldhamer and other skilled musculoskeletal physiologists, orthopaedic surgeons, statisticians and engineers at the University of Connecticut, to gain the necessary scientific skills and career development to advance her research line to a new level. Dr. Lepley’s long-term career goal is to lead a research team focused on developing evidence-based strategies to prevent the development of post-traumatic osteoarthritis (PTOA). The training provided by this K01 would provide her with the needed support to become a productive independent scientist who is able to measure the inflammatory, neural, and morphological responses of muscle and alterations in bone and cartilage health to traumatic joint injury and subsequent rehabilitation strategies. The central tenant of this K01 is to identify rehabilitation strategies capable of promoting muscle and joint health after anterior cruciate ligament (ACL) injury. To date, concentric exercise is the standard mode of exercise prescription after ACL injury. Yet, multiple systematic reviews have shown that concentric exercise does not restore muscle strength and does not deter the onset of PTOA. Emerging evidence suggests that mechanical stress achieved via eccentric exercise is required to initiate strain-sensing molecules that promote the recovery of muscle. We have recently demonstrated that embedding eccentric exercise into a rehabilitation program early after ACL reconstruction promotes the recovery of quadriceps strength better than concentric exercise. Though promising, eccentric exercise is often avoided clinically, as the notion that eccentric exercise is associated with muscle injury has been perpetuated in the literature, and the underlying benefits of eccentrics to muscle remain undefined. Further, the ability of eccentric exercise to prevent the development of PTOA in a high-risk population has never been studied. To provide the evidence-based data needed to support the incorporation of eccentric exercise into rehabilitation, we will establish a non-invasive, clinically-translatable, ACL injury in a rat model and describe the time course of biomechanical alterations, inflammatory response and PTOA progression (aim 1). We will then use this model to report the effectiveness of eccentric exercise to treat muscle weakness (aim 2) and promote bone and cartilage health after ACL injury (aim 3). The central hypothesis is that eccentric exercise will attenuate deficits in neural activity and alterations in muscle morphology, thereby restoring quadriceps strength and promoting joint health more effectively than the current standard of care of concentric exercise after ACL injury. The rationale for conducting this in vivo research, which establishes the physiological benefits of this rehabilitation strategy, is to ultimately inform the development of future clinical trials and generate essential new skills that will promote Dr. Lepley’s independent research program.

项目概要 K01 指导研究科学家发展奖的目的是推广 Lindsey Lepley 博士的由 David Goldhamer 博士和其他熟练的肌肉骨骼专家培训的独立研究计划康涅狄格大学的生理学家、整形外科医生、统计学家和工程师，以获得必要的科学技能和职业发展，将莱普利博士的研究线提升到一个新的水平。长期职业目标是领导一个研究团队，专注于制定基于证据的策略来预防 K01 提供的培训将为她提供预防创伤后骨关节炎 (PTOA) 的机会。获得所需的支持，成为一名富有成效的独立科学家，能够测量肌肉的炎症、神经和形态反应以及骨和软骨健康的改变 K01 的核心内容是确定创伤性关节损伤和随后的康复策略。能够促进前十字韧带 (ACL) 术后肌肉和关节健康的康复策略迄今为止，同心运动是 ACL 损伤后运动处方的标准模式。系统评价表明，向心运动并不能恢复肌肉力量，也不能阻止肌肉力量。新出现的证据表明，通过离心运动获得的机械应力是我们最近发现了启动促进肌肉恢复的应变感应分子所需的物质。在 ACL 重建后早期将离心运动纳入康复计划虽然有希望，但离心运动比向心运动更能促进股四头肌力量的恢复。临床上经常避免运动，因为离心运动与肌肉损伤有关的观念已被人们所接受。这种现象在文献中一直存在，而离心运动对肌肉的潜在好处仍然不明确。此外，离心运动预防高危人群发生 PTOA 的能力已得到证实。从未被研究过，以提供支持纳入怪人所需的循证数据。将运动融入康复中，我们将在大鼠模型中建立非侵入性、可临床转化的 ACL 损伤模型并描述生物力学改变、炎症反应和 PTOA 进展的时间过程（目标 1）然后我们将使用该模型来报告离心运动治疗肌肉无力的有效性（目标）。 2) 促进 ACL 损伤后的骨骼和软骨健康（目标 3）。运动将减轻神经活动的缺陷和肌肉形态的改变，从而恢复比目前的同心圆护理标准更有效地增强股四头肌力量并促进关节健康 ACL 损伤后进行运动的基本原理，该研究建立了生理学基础。这种康复策略的好处是最终为未来临床试验的发展提供信息培养重要的新技能，以促进莱普利博士的独立研究计划。