Restoration of movement following spinal cord injury (SCI) has been achieved using electrical stimulation of peripheral nerves and skeletal muscles. However, practical limitations such as the rapid onset of muscle fatigue hinder clinical application of these technologies. Recently, direct stimulation of alpha motor neurons has shown promise for evoking graded, controlled, and sustained muscle contractions in rodent and feline animal models while overcoming some of these limitations. However, small animal models are not optimal for the development of clinical spinal stimulation techniques for functional restoration of movement. Furthermore, variance in surgical procedure, targeting, and electrode implantation techniques can compromise therapeutic outcomes and impede comparison of results across studies. Herein, we present a protocol and large animal model that allow standardized development, testing, and optimization of novel clinical strategies for restoring motor function following spinal cord injury. We tested this protocol using both epidural and intraspinal stimulation in a porcine model of spinal cord injury, but the protocol is suitable for the development of other novel therapeutic strategies. This protocol will help characterize spinal circuits vital for selective activation of motor neuron pools. In turn, this will expedite the development and validation of high-precision therapeutic targeting strategies and stimulation technologies for optimal restoration of motor function in humans.

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Introduction Regional variability in interstitial fluid pressure confounds use of intramuscular pressure measurement to assess muscle force. It is hypothesized that interstitial flow is dependent on intramuscular pressure. The goal of this study was to assess the feasibility of using fluorescent microspheres to evaluate movement of interstitial fluid in skeletal muscle. Methods Two diameters of fluorescent microspheres were injected into the rat tibialis anterior during both static (n=6) and passively lengthened (10% strain) experimental conditions (n=6). Microsphere dispersion was evaluated using confocal imaging of transverse muscle sections. Results Confocal microscopy fluorescent microspheres tracked interstitial fluid while not penetrating the muscle fiber. When compared to the static condition, significantly greater dispersion (P=0.003) was seen with passively lengthened conditions (17±9% vs 31±7%, respectively). Dispersion did not differ for the 2 microsphere sizes (P=0.811). Discussion Fluorescent microspheres track movement of interstitial fluid, and dispersion is dependent on passive lengthening.

The current method of measuring arthrofibrosis in live rabbits is critically limited. Specifically, this method involves radioactive fluoroscopy, error-prone goniometric measurements, and static joint angle outcomes that fail to approximate the compliance of tissues surrounding the joint. This study aims to validate a novel method of capturing the compliance of contracted tissues surrounding the joint without the use of fluoroscopy or animal sacrifice. Surgically induced contractures of one-hundred and eight rabbits were measured using the current standard of contracture measurement (a pulley system) as well as a newly designed dynamic load cell (DLC) device. The DLC device was highly reliable when compared to the pulley system (r = 0.907, p < 0.001). Finally, the DLC device produced joint stiffness hysteresis curves capable of approximating the compliance of stiff joint tissues, ultimately calculating a mean joint stiffness of 1.57 ± 1.31 N · m · rad (range, 0.33-6.37 N · m · rad ). In conclusion, the DLC device represents a valid method for measuring joint contractures. Further, the DLC device notably improves current techniques by introducing the capacity to approximate the compliance of contracted tissues in living rabbits. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.