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ABSTRACT: Upper extremity neuromuscular electrical stimulation (FNS) has long been utilized as a neuroprosthesis to restore hand-grasp function in individuals with neurological disorders and injuries. More recently, electrical stimulation is being used as a rehabilitative therapy to tap into central nervous system plasticity. Here, we present initial development of a rodent model for neuromuscular stimulation induced forelimb movement that can be used as a platform to investigate stimulation-induced plasticity. The motor points for flexors and extensors of the shoulder, elbow, and digits were identified and implanted with custom-built stimulation electrodes. The strength-duration curves were determined and from these curves the appropriate stimulation parameters required to produce consistent isolated contraction of each muscle with adequate joint movement were determined. Using these parameters and previous locomotor EMG data, stimulation was performed on each joint muscle pair to produce reciprocal flexion/extension movements in the shoulder, elbow, and digits, while 3D joint kinematics were assessed. Additionally, co-stimulation of multiple muscles across multiple forelimb joints was performed to produce stable multi-joint movements similar to those observed during reach-grasp-release movements. Future work will utilize this model to investigate the efficacy and underlying mechanisms of forelimb neuromuscular stimulation therapy to promote recovery and plasticity after neural injury in rodents.
Journal of Neuroscience Methods 02/2008; 167(2):317-26. · 1.98 Impact Factor
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ABSTRACT: The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies.
The Journal of Rehabilitation Research and Development 02/2008; 45(2):229-40. · 1.78 Impact Factor
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ABSTRACT: Transplantation of growth-permissive cells or tissues was used to bridge a lesion cavity and induce axonal growth in experimental spinal cord injury (SCI). Axonal interactions between host and transplant may be affected by upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) following various transplantation strategies. The extent of axonal growth and functional recovery after transplantation of embryonic spinal cord tissue decreases in adult compared to neonatal host. We hypothesized that CSPGs contribute to the decrease in the extent to which transplant supports axonal remodeling and functional recovery. Expression of CSPGs increased after overhemisection SCI in adult rats but not in neonates. Embryonic spinal cord transplant was surrounded by CSPGs deposited in host cord, and the interface between host and transplant seemed to contain a large amount of CSPGs. Intrathecally delivered chondroitinase ABC (C'ase) improved recovery of distal forelimb usage and skilled motor behavior after C4 overhemisection injury and transplantation in adults. This behavioral recovery was accompanied by an increased amount of raphespinal axons growing into the transplant, and raphespinal innervation to the cervical motor region was promoted by C'ase plus transplant. Moreover, C'ase increased the number of transplanted neurons that grew axons to the host cervical enlargement, suggesting that degradation of CSPGs supports remodeling not only of host axons but also axons from transplanted neurons. Our results suggest that CSPGs constitute an inhibitory barrier to prevent axonal interactions between host and transplant in adults, and degradation of the inhibitory barrier can potentiate transplant-mediated axonal remodeling and functional recovery after SCI.
The Journal of Comparative Neurology 08/2006; 497(2):182-98. · 3.81 Impact Factor
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ABSTRACT: The adult central nervous system is capable of considerable anatomical reorganization and functional recovery after injury. Functional outcomes, however, vary greatly, depending upon size and location of injury, type and timing of intervention, and type of recovery and plasticity evaluated. The present study was undertaken to assess the recovery of skilled and unskilled forelimb function in adult rats after a C5/C6 spinal cord over-hemisection and delayed intervention with fetal spinal cord transplants and neurotrophins. Recovery of forelimb function was evaluated during both target reaching (a skilled behavior) and vertical exploration (an unskilled behavior). Anatomical tracing and immunohistochemistry were used to assess the growth of descending raphespinal, corticospinal, and rubrospinal fibers at the injury site, tracts that normally confer forelimb function. Delayed intervention with transplants and either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) restored skilled left forelimb reaching to pre-injury levels. Animals showed recovery of normal reaching movements rather than compensation with abnormal movements. Transplants and NT-3 also improved right forelimb use during an unskilled vertical exploration, but not skilled right reaching. Intervention with fetal transplant tissue supported the growth of descending serotonergic, corticospinal, and rubrospinal fibers into the transplant at the lesion site. The addition of neurotrophins, however, did not significantly increase axonal growth at the lesion site. These studies suggest that the recovery of skilled and unskilled forelimb use is possible after a large cervical spinal cord injury following delayed intervention with fetal spinal cord and neurotrophins. Plasticity of both spared and axotomized descending pathways likely contributes to the functional recovery observed.
Journal of Neurotrauma 06/2006; 23(5):617-34. · 3.65 Impact Factor