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的方式执行各种运动任务，例如运动。一个系统组成部分的损伤，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，可导致其他系统组成部分的长期继发性变化。在某些情况下，这些次要变化可能是不适应的，因此导致功能能力进一步下降；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，一系列未损伤和不完全脊髓损伤（iSCI）啮齿动物的实验研究将推动啮齿动物后肢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后受损的中枢驱动、脊髓反射和肌肉骨骼变化之间复杂相互作用在适当治疗设计中的作用。

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.