Repeated epidural stimulation modulates cervical spinal cord excitability in healthy adult rats.

Spinal evoked motor responses (SEMR) are utilized in longitudinal pre-clinical and human studies to reflect the in-vivo physiological changes in neural networks secondary to a spinal cord injury (SCI) or neuro-rehabilitative treatments utilizing epidural stimulation (ES). However, it remains unknown whether the repeated ES exposure during SEMR testing itself modulates spinal cord physiology and accompanying SEMR characteristics. To answer this, ES was delivered to the cervical spinal cord using standard stimulation paradigms during multiple SEMR data acquisition sessions (~ 17 h spanning across 100 days) in ten healthy adult rats.

Novel comprehensive analysis of skilled reaching and grasping behavior in adult rats.

Background: Reaching and grasping (R&G) in rats is commonly used as an outcome measure to investigate the effectiveness of rehabilitation or treatment strategies to recover forelimb function post spinal cord injury. Kinematic analysis has been limited to the wrist and digit movements. Kinematic profiles of the more proximal body segments that play an equally crucial role in successfully executing the task remain unexplored.

In vivo electrophysiological mechanisms underlying cervical epidural stimulation in adult rats.

Key Points: To electrophysiologically determine the predominant neural structures activated with cervical epidural stimulation (ES), well-established electrophysiological protocols (single-pulse, paired-pulse and multiple frequency stimulation) were delivered at rest, during motor activity and under anaesthesia in adult rats. Cervical ES resulted in spinal evoked motor responses with three different waveforms - early response (ER), middle response (MR) and late response (LR). ERs remained unmodulated by repeated stimulation protocols.

3D Kinematic Gait Analysis for Preclinical Studies in Rodents.

The utility of three-dimensional (3D) kinematic motion analysis systems is limited in rodents. Part of the reason for this inadequacy is the use of complex algorithms and mathematical modeling that accompany 3D data collection and analysis procedures. This work provides a simple, user-friendly, step-by-step detailed methodology for 3D kinematic gait analysis during treadmill locomotion in healthy and neurotraumatic rats using a six-camera motion capture system.

Rostral lumbar segments are the key controllers of hindlimb locomotor rhythmicity in the adult spinal rat.

The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influence in rhythm initiation and generation.

Novel Speed-Controlled Automated Ladder Walking Device Reveals Walking Speed as a Critical Determinant of Skilled Locomotion after a Spinal Cord Injury in Adult Rats.

The horizontal ladder task is an established method to assess skilled locomotor recovery after neurological dysfunction. Walking speed is often used as a standardized measure in locomotor assessment of overground walking in human and pre-clinical studies, but the assessment of walking speed is typically ignored during skilled locomotor tasks. Ample empirical evidence indicates that walking speeds on the horizontal ladder are largely non-uniform after central nervous system trauma, suggesting that it could pose a potential source of variability in assessing motor deficits.

Development of an Activity-Dependent Epidural Stimulation System in Freely Moving Spinal Cord Injured Rats: A Proof of Concept Study.

Extensive pre-clinical and clinical experimentation has yielded data on the robustness and versatility of epidural stimulation (ES) strategies to activate spinal neural circuitry to produce functional benefits. Increasing studies are now reporting that closed-loop electrical stimulation delivery methods significantly enhance the neuromodulation effects of stimulation, to in turn, improve physiological outcomes of the intervention. No studies have yet explored the feasibility and usage of closed-loop systems to neuromodulate the cervical spinal cord using ES.

Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats.

Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful hindlimb stepping in spinal rats.

Unique Spatiotemporal Neuromodulation of the Lumbosacral Circuitry Shapes Locomotor Success after Spinal Cord Injury.

Spinal cord epidural stimulation has resulted in the initiation of voluntary leg movements and improvement in postural, bladder, and sexual function. However, one of the limitations in reaching the full potential of epidural stimulation for therapeutic purposes in humans has been the identification of optimal stimulation configurations that can neuromodulate the spinal cord for stepping. In the present work, we investigated the mechanisms underlying the specificity of interaction between the rostral and caudal spinal cord circuitries in enabling locomotion in spinal rats (n = 10) by epidural spinal cord stimulation.

Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats.

Background: Epidural spinal cord stimulation is a promising technique for modulating the level of excitability and reactivation of dormant spinal neuronal circuits after spinal cord injury (SCI). We examined the ability of chronically implanted epidural stimulation electrodes within the cervical spinal cord to (1) directly elicit spinal motor evoked potentials (sMEPs) in forelimb muscles and (2) determine whether these sMEPs can serve as a biomarker of forelimb motor function after SCI.

New Method: We implanted EMG electrodes in forelimb muscles and epidural stimulation electrodes at C6 and C8 in adult rats.

Plasticity of subcortical pathways promote recovery of skilled hand function in rats after corticospinal and rubrospinal tract injuries.

The corticospinal and rubrospinal tracts are the predominant tracts for controlling skilled hand function. Injuries to these tracts impair grasping but not gross motor functions such as overground locomotion. The aim of the present study was to determine whether or not, after damage to both the corticospinal and rubrospinal tracts, other spared subcortical motor pathway can mediate the recovery of skilled hand function.

In vivo (31)P NMR spectroscopy assessment of skeletal muscle bioenergetics after spinal cord contusion in rats.

Purpose: Muscle paralysis after spinal cord injury leads to muscle atrophy, enhanced muscle fatigue, and increased energy demands for functional activities. Phosphorus magnetic resonance spectroscopy ((31)P-MRS) offers a unique non-invasive alternative of measuring energy metabolism in skeletal muscle and is especially suitable for longitudinal investigations. We determined the impact of spinal cord contusion on in vivo muscle bioenergetics of the rat hind limb muscle using (31)P-MRS.

Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.

Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats.

Variability in step training enhances locomotor recovery after a spinal cord injury.

Performance of a motor task is improved by practicing a specific task with added 'challenges' to a training regimen. We tested the hypothesis that, in the absence of brain control, the performance of a motor task is enhanced by training using specific variations of that task. We utilized modifications of step performance training to improve the ability of spinal rats to forward step.

Rodent estrous cycle response to incomplete spinal cord injury, surgical interventions, and locomotor training.

Estrous cycle disruption after spinal cord injury (SCI) in female rats is a common phenomenon. It remains unknown, however, if the aberrant estrous cycle is a result of an injury to the spinal cord itself or due to the general stress associated with surgical interventions. We addressed this issue by determining estrous cyclicality in female rats after a spinal cord hemisection (HX), implantation of EMG wires into selected hind limb muscles, and/or injections of tracer dyes into the spinal cord.

Lower-extremity muscle cross-sectional area after incomplete spinal cord injury.

Objectives: (1) To quantify skeletal muscle size in lower-extremity muscles of people after incomplete spinal cord injury (SCI), (2) to assess differences in muscle size between involved lower limbs, (3) to determine the impact of ambulatory status (using wheelchair for community mobility vs not using a wheelchair for community mobility) on muscle size after incomplete SCI, and (4) to determine if differential atrophy occurs among individual muscles after incomplete SCI.

Design: Case-control study.

Setting: University research setting.

Eshkol-Wachman movement notation in diagnosis: the early detection of Asperger's syndrome.

The diagnostic criteria of Asperger's syndrome (AS), considered a part of the autistic spectrum disorder, are still unclear. A critical marker, which distinguishes AS from autism, is the presence of language. The ability of a child with AS to acquire and use language early results in the fact that AS usually is diagnosed much later than autism.