CRCNS: Modeling Neuromusculoskeletal Alterations after Spinal Cord Injury

描述（由申请人提供）：神经和肌肉骨骼系统之间的相互作用使我们能够以稳健和适应性强的方式执行各种运动任务，例如运动。一个系统组件的损伤，例如创伤性脊髓损伤，由于其密切的相互作用和固有的可塑性，可能导致其他系统组件的长期继发性变化。在某些情况下，这些继发性变化可能是适应不良的，因此导致功能能力进一步降低;在其他情况下，这些变化可能是有利的，因此导致功能恢复。在这项工作中，在未受伤和不完全脊髓损伤（iSCI）啮齿动物的一系列实验研究将推动啮齿动物后肢的生物力学和神经控制的详细数学模型的发展。该模型将用于研究iSCI后中枢驱动受损、脊髓反射和肌肉骨骼变化之间复杂相互作用在设计适当治疗中的作用。 具体而言，将使用慢性啮齿动物胸挫伤脊髓损伤制备物来研究脊髓运动神经元的内在细胞内电生理学及其传入控制以及iSCl后存在的内在肌肉骨骼特性。实验数据将指导神经和动态肌肉骨骼组件的计算模型的开发。Hodgkin-Huxley型神经元表示将用于模拟局部脊髓神经回路，包括运动神经元、中间神经元和参与特定脊髓反射的传入神经元。肌肉骨骼模型将结合实验确定的几何肌肉肌腱路径，惯性属性，肌纤维属性，和3D激光扫描骨表面几何形状。因此，该综合模型将用于测试有关特定离子电流、改变的中枢驱动、改变的肌肉骨骼特性和改变的感觉反射增益对iSCI后肢体运动控制的作用的假设。这项工作的成功完成将提供新的信息，可以帮助指导有效的治疗技术和适当的康复治疗的发展，以提高功能性运动恢复和生活质量的一些200，000人目前生活在脊髓损伤相关的流动性，就业能力和二级健康相关的限制在美利坚合众国。

DESCRIPTION (provided by applicant): The interaction between neural and musculoskeletal systems enables us to perform a variety of motor tasks, such as locomotion, in a robust and adaptable manner. Damage to one system component, e.g. traumatic spinal cord injury, can lead to long-term secondary changes in other system components due to their close interactions and their inherent plasticity. In some instances, these secondary changes may be maladaptive, and therefore result in further reduction in functional capacity; in other instances, the changes may be favorable, and therefore result in recovery of function. In this work, a series of experimental studies in uninjured and incomplete spinal cord inured (iSCI) rodents will drive the development of a detailed mathematical model of the biomechanics and neural control of the rodent hindlimb. This model will be used to investigate the role of complex interactions amongst impaired central drive, spinal reflexes and musculoskeletal changes after iSCI in the design of appropriate therapy. Specifically, a chronic rodent thoracic contusion spinal cord injury preparation will be used to investigate the intrinsic intracellular electrophysiology of spinal motoneurons and their afferent control and the intrinsic musculoskeletal properties present after iSCl. The experimental data will guide development of a computational model with neural and dynamic musculoskeletal components. Hodgkin-Huxley type neuron representations will be used to model the local spinal neural circuits that include motoneurons, interneurons and afferents involved in specific spinal reflexes. The musculoskeletal model will incorporate experimentally-determined geometrical musculotendon paths, inertial properties, muscle fiber properties, and 3D laser scanned bony surface geometries. The comprehensive model will consequently be used to test hypotheses regarding the roles of specific ionic currents, altered central drive, altered musculoskeletal properties and altered sensory reflex gain on control of limb movement after iSCI. Successful completion of the work will provide novel information that could help guide the development of efficient treatment techniques and appropriate rehabilitative therapies for enhancing functional locomotor recovery and quality of life for some of the 200,000 people currently living with spinal cord injury related mobility, employability and secondary health related limitations in the United States of America.