Respiratory Training and Plasticity After Cervical Spinal Cord Injury.
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ABSTRACT:
SUBMITTER: Randelman M
PROVIDER: S-EPMC8490715 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord injury (SCI) for studying respiratory dysfunction and plasticity. However, most previous studies were performed under anesthesia, which significantly alters respiratory network. Therefore, the goal of this work was to assess spontaneous diaphragm recovery post-C2Hx in awake, freely behaving animals. Adult rats were chronically implanted with diaphragm EMG electrodes and recorded during 8 weeks post-C2Hx. Our results reveal that ipsilateral diaphragm activity partially recovers within days post-injury and reaches pre-injury amplitude in a few weeks. However, the full extent of spontaneous ipsilateral recovery is significantly attenuated by anesthesia (ketamine/xylazine, isoflurane, and urethane). This suggests that the observed recovery may be attributed in part to activation of NMDA receptors which are suppressed by anesthesia. Despite spontaneous recovery in awake animals, ipsilateral hemidiaphragm dysfunction still persists: i) Inspiratory bursts during basal (slow) breathing exhibit an altered pattern, ii) the amplitude of sighs - or augmented breaths - is significantly decreased, and iii) the injured hemidiaphragm exhibits spontaneous events of hyperexcitation. The results from this study offer an under-appreciated insight into spontaneous diaphragm activity and recovery following high cervical spinal cord injury in awake animals.
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Project description:In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.
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Project description:Motor dysfunction and muscle atrophy are well documented in the lower extremity after spinal cord injury. However, the extent and time course of myoplastic changes in forelimb musculature is not clear.Forelimb muscle morphology and fiber type were evaluated after high cervical hemilesion injury in rats.There was significant atrophy of the ipsilateral extensor carpi radialis longus (ECRL) muscle at 2 weeks postinjury, which was subsequently reversed at 8 weeks postinjury. The triceps muscle showed minimal evidence of atrophy after spinal injury. No significant changes in fiber type were observed.These findings indicate a robust capacity for spontaneous myoplasticity after C2 hemisection injury but highlight differential capacity for plasticity within the forelimb muscles.
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Project description:The neural plasticity of spinal reflexes after two contrasting forms of walking training was determined in individuals with chronic, motor-incomplete spinal cord injury (SCI). Endurance Training involved treadmill walking for as long as possible, and Precision Training involved walking precisely over obstacles and onto targets overground. Twenty participants started either Endurance or Precision Training for 2 months and then crossed over after a 2-month rest period to the other form of training for 2 months. Measures were taken before and after each phase of training and rest. The cutaneomuscular reflex (CMR) during walking was evoked in the soleus (SOL) and tibialis anterior muscles by stimulating the posterior tibial nerve at the ankle. Clonus was estimated from the EMG power in the SOL during unperturbed walking. The inhibitory component of the SOL CMR was enhanced after Endurance but not Precision Training. Clonus did not change after either form of training. Participants with lower reflex excitability tended to be better walkers (i.e., faster walking speeds) prior to training, and the reduction in clonus was significantly correlated with the improvement in walking speed and distance. Thus, reflex excitability responded in a training-specific way, with the reduction in reflex excitability related to improvements in walking function. Trial registration number is NCT01765153.
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Project description:Cervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI.
| S-EPMC7794462 | biostudies-literature
Project description:Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord. We developed spinal cord associative plasticity, precisely timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen the sensorimotor connections in the spinal cord and improve recovery after spinal cord injury. We tested physiological effects of paired stimulation, the pathways that mediate it, and its function in a preclinical trial. Subthreshold spinal cord stimulation strongly augmented motor cortex evoked muscle potentials at the time they were paired, but only when they arrived synchronously in the spinal cord. This paired stimulation effect depended on both cortical descending motor and spinal cord proprioceptive afferents; selective inactivation of either of these pathways fully abrogated the paired stimulation effect. Spinal cord associative plasticity, repetitive pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability for hours after pairing ended. To apply spinal cord associative plasticity as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that spared connections after moderate spinal cord injury were sufficient to support plasticity. In a blinded trial, rats received a moderate C4 contusive spinal cord injury. Ten days after injury, they were randomized to 30 min of spinal cord associative plasticity each day for 10 days or sham stimulation. Rats with spinal cord associative plasticity had significantly improved function on the primary outcome measure, a test of dexterity during manipulation of food, at 50 days after spinal cord injury. In addition, rats with spinal cord associative plasticity had persistently stronger responses to cortical and spinal stimulation than sham stimulation rats, indicating a spinal locus of plasticity. After spinal cord associative plasticity, rats had near normalization of H-reflex modulation. The groups had no difference in the rat grimace scale, a measure of pain. We conclude that spinal cord associative plasticity strengthens sensorimotor connections within the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Since both motor cortex and spinal cord stimulation are performed routinely in humans, this approach can be trialled in people with spinal cord injury or other disorders that damage sensorimotor connections and impair dexterity.
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Project description: Not available
| S-EPMC6583212 | biostudies-literature
Project description:Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.
| S-EPMC7266985 | biostudies-literature
Project description:Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and ?-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.
| S-EPMC5509620 | biostudies-literature
Project description:Introduction Degenerative Cervical Myelopathy [DCM] is a slow-motion spinal cord injury. Compression and dynamic compression have been considered disease hallmarks. However, this is likely an oversimplification, as compression is more commonly incidental and has only modest correlation to disease severity. MRI studies have recently suggested spinal cord oscillation could play a role. Research question To determine if spinal cord oscillation could contribute to spinal cord injury in degenerative cervical myelopathy. Material and methods A computational model of an oscillating spinal cord was developed from imaging of a healthy volunteer. Using finite element analysis, the observed implications of stress and strain, were measured in the context of a simulated disc herniation. The significance was bench marked by comparison to a more recognised dynamic injury mechanism; a flexion extension model of dynamic compression. Results Spinal cord oscillation altered both compressive and shear strain on the spinal cord. Following initial compression, compressive strain moves from within the spinal cord to the spinal cord surface, whilst shear strain is magnified by 0.1–0.2, depending on the amplitude of oscillation. These orders of magnitude are equivalent to a dynamic compression model. Discussion and conclusion Spinal cord oscillation could significantly contribute to spinal cord damage across DCM. Its repeated occurrence with every heartbeat, draws parallels to the concept of fatigue damage, which could reconcile differing theories on the origins of DCM. This remains hypothetical at this stage, and further investigations are required. Highlights • Aetiology of Degenerative Cervical Myelopathy is poorly understood• Paradigm based purely on ‘compression’ could be an oversimplification• Analysis of a computational model based on an MRI cervical spine• Loading from cord oscillation was equivalent to that from dynamic compression• Proposes a cause of ‘repetitive microtrauma’ warranting further investigation
| S-EPMC10293319 | biostudies-literature