EMRSHN: Exploring the modulatory role of sex hormones along the neuromechanical axis in females

肌肉骨骼损伤的发生率在男性和女性之间有很大的不同，前部的发生率 十字韧带(ACL)损伤在女运动员中高达9倍。这些伤害会导致短期和长期的- 长期健康问题，包括从学校或工作中损失的时间，心理困扰，以及受伤后的关节 骨性关节炎。性激素可能对这种伤害差异有很大影响：伤害率 差异在青春期之前并不明显，损伤发生在月经前半段的比例更大。 周而复始。虽然大多数研究都集中在肌肉骨骼系统的被动组件上，但他们认为 女性激素浓度的波动可能会改变韧带本身的机械性能，直接 韧带松弛和前交叉韧带损伤之间的联系尚未得到证实。这项提案的目标是测试我们的 中心假设：性激素浓度的变化会导致运动的基本要素发生变化 控制-在多个层面上，从肌腱单位到运动控制电路。在我们的预赛中 数据显示，在肌肉水平上，当雌二醇时，肌肉反射反应最低。 浓度最高，膝前松弛没有变化。在脊椎回路层面，我们已经展示了 虽然激素浓度的日常变化不会调节脊髓运动神经元的兴奋性，但 服用口服避孕药的女性总体兴奋性水平较低。最后，在大脑层面上， 我们已经证明，当雌二醇时，皮质内神经元间回路的兴奋性增加。 浓度最高。在我们提案的目标1和目标2中，日常测试将前所未有地允许详细的 评估荷尔蒙浓度与肌肉和肌肉的变化之间的特定时间关系 放松状态和活动状态下的脊椎水平。在目标3中，每日荷尔蒙浓度将特别 确定每个受试者的测试日期，引导有针对性的评估发挥波动激素的作用 浓度对皮质兴奋性的影响。在目标1中，我们将确定性激素波动对 肌肉在主动和被动状态下的拉伸反射，以及激素浓度之间的时差 变化和反射反应。我们将使用一个技术简单的评估，该评估可以在 菲尔德。在目标2中，我们将确定性激素波动对脊髓运动神经元兴奋性的影响。 以H反射为探头，以肌肉抽动反应同步变化肌力。 目标1和2将重点放在口服避孕药的不同作用上。在目标3中，我们将使用成对脉冲 经颅磁刺激对主动收缩时性激素的影响 自然骑自行车的女性大脑皮质兴奋性的波动。我们的发现有可能指导未来 研究伤害预防策略，包括有针对性的神经肌肉训练。这一知识将会 使临床医生能够在高潮时期教育女性患者性激素对神经肌肉的影响 波动，包括青春期、怀孕和更年期。

The rate of musculoskeletal injury differs substantially between men and women, with the incidence of anterior cruciate ligament (ACL) injuries up to 9 times higher in female athletes. These injuries cause short- and long- term health problems, including time lost from school or work, psychological distress, and post-injury joint osteoarthritis. Sex hormones may make a significant contribution to this injury disparity: injury rate differences are not evident until puberty, and injuries occur disproportionately in the first half of the menstrual cycle. While most research has focused on passive components of the musculoskeletal system, arguing that female fluctuating hormone concentrations may change mechanical properties of the ligament itself, a direct link between ligament laxity and ACL injury has not been proven. The goal of this proposal is to test our central hypothesis that changes in sex hormone concentration result in changes to the basic elements of motor control – at multiple levels, from the musculotendinous unit to motor control circuitry. In our preliminary data, at the muscle level, we have shown that the muscle reflex response is lowest when estradiol concentrations are highest, with no change in anterior knee laxity. At the spinal circuitry level, we have shown that while day-to-day changes in hormone concentration do not modulate spinal motor neuronal excitability, a lower overall level of excitability exists in women who take oral contraceptives. Finally, at the level of the brain, we have shown the excitability of intra-cortical interneuronal circuits is increased when estradiol concentrations are highest. In Aims 1 & 2 of our proposal, daily testing will allow, as never-before, a detailed assessment of the time-specific relationship between hormone concentration and changes at the muscle and spinal level during both relaxed and active states. In Aim 3, daily hormone concentrations will specifically determine each subject's testing day, guiding targeted assessments into the role of fluctuating hormone concentrations on cortical excitability. In Aim 1 we will determine the influence of sex hormone fluctuations on the muscle stretch reflex during active and passive states, and the time-lag between hormone concentration changes and the reflex response. We will use a technically simple assessment that could be implemented in the field. In Aim 2 we will determine the influence of sex hormone fluctuations on spinal motor neuron excitability using H-reflex as a probe and the simultaneous change in the muscle mechanics using muscle twitch response. Aims 1 & 2 will include a focus on the differential role of oral contraceptives. In Aim 3 we will use paired-pulse transcranial magnetic stimulation during active contraction to determine the influence of sex hormone fluctuations on cortical excitability in naturally cycling women. Our findings have the potential to guide future research in injury prevention strategies, including targeted neuromuscular training. This knowledge will enable clinicians to educate female patients on neuromuscular effects of sex hormones during times of high fluctuations, including puberty, pregnancy, and menopause.