Objective Spinal cord injury causes a drastic loss of motor, sensory and autonomic function. The goal of this project was to investigate the use of intraspinal microstimulation (ISMS) for producing long distances of walking over ground. ISMS is an electrical stimulation method developed for restoring motor function by activating spinal networks below the level of an injury. It produces movements of the legs by stimulating the ventral horn of the lumbar enlargement using fine penetrating electrodes (≤ 50µm diameter). Approach In each of five adult cats (4.2–5.5kg), ISMS was applied through 16 electrodes implanted with tips targeting lamina IX in the ventral horn bilaterally. A desktop system implemented a physiologically-based control strategy that delivered different stimulation patterns through groups of electrodes to evoke walking movements with appropriate limb kinematics and forces corresponding to swing and stance. Each cat walked over an instrumented 2.9m walkway and limb kinematics and forces were recorded. Main Results Both propulsive and supportive forces were required for over-ground walking. Cumulative walking distances ranging from 609m to 835m (longest tested) were achieved in three animals. In these three cats, the mean peak supportive force was 3.5±0.6N corresponding to full-weight-support of the hind legs, while the angular range of the hip, knee, and ankle joints were 23.1±2.0°, 29.1±0.2°, and 60.3±5.2°, respectively. To further demonstrate the viability of ISMS for future clinical use, a prototype implantable module was successfully implemented in a subset of trials and produced comparable walking performance. Significance By activating inherent locomotor networks within the lumbosacral spinal cord, ISMS was capable of producing bilaterally coordinated and functional over-ground walking with current amplitudes <100 µA. These exciting results suggest that ISMS may be an effective intervention for restoring functional walking after spinal cord injury.
The overall goal of this work was to create a high-resolution MRI atlas of the lumbosacral enlargement of the spinal cord of the rat (Sprague–Dawley), cat, domestic pig, rhesus monkey, and human. These species were chosen because they are commonly used in basic and translational research in spinal cord injuries and diseases. Six spinal cord specimens from each of the studied species (total of 30 specimens) were fixed, extracted, and imaged. Sizes of the spinal cord segments, cross-sectional dimensions, and locations of the spinal cord gray and white matter were quantified and compared across species. The lumbar enlargement spans spinal cord levels L3-S1 in rats, L4-S1 in cats, L3-S1 in pigs, L2/L3-L7/S1 in monkeys, and T12/L1-S1/S2 in humans. The enlargements in pigs and humans are largest and most similar in size (length and cross-sectional area); followed by monkeys and cats; and followed by rats. The obtained atlas establishes a neuroanatomical reference for the intact lumbosacral spinal cord in these species. It can also be used to guide the planning of surgical procedures of the spinal cord and technology design and development of spinal cord neuroprostheses, as well as precise delivery of cells/drugs into target regions within the spinal cord parenchyma.
Spinal cord injury (SCI) leads to chronic and multifaceted disability, which severely impacts the physical and mental health as well as the socio-economic status of affected individuals. Permanent disabilities following SCI result from the failure of injured neurons to regenerate and rebuild functional connections with their original targets. Inhibitory factors present in the SCI microenvironment and the poor intrinsic regenerative capacity of adult spinal cord neurons are obstacles for regeneration and functional recovery. Considerable progress has been made in recent years in developing cell and molecular approaches to enable the regeneration of damaged spinal cord tissue. In this review, we highlight several potent cell-based approaches and genetic manipulation strategies (gene therapy) that are being investigated to reconstruct damaged or lost spinal neural circuits and explore emerging novel combinatorial approaches for enhancing recovery from SCI.
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