CRCNS: Modeling Neuromusculoskeletal Alterations after Spinal Cord Injury

描述(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健壮和适应性强的方式执行各种运动任务，如运动。一个系统组件的损伤，如创伤性脊髓损伤，可导致其他系统组件的长期继发性变化，因为它们之间的密切相互作用和固有的可塑性。在某些情况下，这些继发性改变可能是不适应的，因此导致功能能力的进一步减少；在其他情况下，这些改变可能是有利的，因此导致功能恢复。在这项工作中，对未损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建立啮齿动物后肢生物力学和神经控制的详细数学模型。该模型将用于研究ISCI后受损的中央驱动力、脊柱反射和肌肉骨骼变化之间的复杂相互作用在设计适当治疗中的作用。 具体地说，慢性啮齿动物胸部挫伤脊髓损伤的制备将被用来研究脊髓运动神经元的内在细胞内电生理及其传入控制，以及iSCL后存在的内在肌肉骨骼特性。实验数据将指导开发包含神经和动态肌肉骨骼组件的计算模型。Hodgkin-Huxley类型的神经元表示将被用来模拟局部脊髓神经回路，包括涉及特定脊髓反射的运动神经元、中间神经元和传入。肌肉骨骼模型将包括实验确定的几何肌腱路径、惯性特性、肌肉纤维特性和3D激光扫描的骨骼表面几何图形。因此，这个综合模型将被用来检验关于特定离子电流、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在控制ISCI后肢体运动方面的作用的假设。这项工作的成功完成将提供新的信息，有助于指导开发有效的治疗技术和适当的康复疗法，以加强功能运动恢复和生活质量，目前美利坚合众国有20万人患有与脊髓损伤有关的行动能力、就业能力和二级健康相关限制。

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.