Ddx20, DEAD-box helicase 20 is essential for maintaining microglial homeostasis.

Objective. The purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation. Approach. Adult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At 4 weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles. Main results. In healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10–12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ∼20 and 60 ms, generally following a Gaussian distribution, rising above baseline at time L ON, followed by a peak response (L p), and then falling below baseline at time L OFF. EMG responses occurred between L ON and L p( 25–27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord neurons after a dorsal midline contusion injury. Significance. This study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

Similarities between the clinical presentation of individuals living with spinal cord injury (SCI) and astronauts are remarkable, and may be of great interest to clinicians and scientists alike. The primary purpose of this review is to outline the manner in which cardiovascular, musculoskeletal, renal, immune and sensory motor systems are affected by microgravity and SCI. A comprehensive review of the literature was conducted (using PubMed) to evaluate the hallmark symptoms seen after spaceflight and SCI. This literature was then examined critically to determine symptoms common to both populations. Both SCI and prolonged microgravity exposure are associated with marked deteriorations in various physiological functions. Atrophy in muscle and bone, cardiovascular disturbances, and alterations in renal, immune and sensory motor systems are conditions commonly observed not only in individuals with SCI, but also in those who experience prolonged gravity unloading. The preponderance of data indicates that similar physiological changes occur in both SCI and prolonged space flight. These findings have important implications for future research in SCI and prolonged space flight.

Activity-dependent plasticity occurs in the spinal cord throughout life. Driven by input from the periphery and the brain, this plasticity plays an important role in the acquisition and maintenance of motor skills and in the effects of spinal cord injury and other central nervous system disorders. The responses of the isolated spinal cord to sensory input display sensitization, long-term potentiation, and related phenomena that contribute to chronic pain syndromes; they can also be modified by both classical and operant conditioning protocols. In animals with transected spinal cords and in humans with spinal cord injuries, treadmill training gradually modifies the spinal cord so as to improve performance. These adaptations by the isolated spinal cord are specific to the training regimen and underlie new approaches to restoring function after spinal cord injury. Descending inputs from the brain that occur during normal development, as a result of supraspinal trauma, and during skill acquisition change the spinal cord. The early development of adult spinal cord reflex patterns is driven by descending activity; disorders that disrupt descending activity later in life gradually change spinal cord reflexes. Athletic training, such as that undertaken by ballet dancers, is associated with gradual alterations in spinal reflexes that appear to contribute to skill acquisition. Operant conditioning protocols in animals and humans can produce comparable reflex changes and are associated with functional and structural plasticity in the spinal cord, including changes in motoneuron firing threshold and axonal conduction velocity, and in synaptic terminals on motoneurons. The corticospinal tract has a key role in producing this plasticity. Behavioral changes produced by practice or injury reflect the combination of plasticity at multiple spinal cord and supraspinal sites. Plasticity at multiple sites is both necessary-to insure continued performance of previously acquired behaviors-and inevitable-due to the ubiquity of the capacity for activity-dependent plasticity in the central nervous system. Appropriate induction and guidance of activity-dependent plasticity in the spinal cord is an essential component of new therapeutic approaches aimed at maximizing function after spinal cord injury or restoring function to a newly regenerated spinal cord. Because plasticity in the spinal cord contributes to skill acquisition and because the spinal cord is relatively simple and accessible, this plasticity is a logical and practical starting point for studying the acquisition and maintenance of skilled behaviors.

Loss of lower limb motor functions is among the most commonly seen effects of spinal cord injuries (SCI). Even with the current modern medical care, SCI patients require intense care at high expense. Animal models used for research on SCI may help develop better and lower cost therapies. It is well known that neonatal rats with complete SCI are capable of generating autonomous lumbar stepping, some even achieve independent weight support when tested as adults. On the contrary, rats injured at adult ages have limited recovery after a complete spinal cord injury. What can account for the difference? We hypothesized that neonatal and adult SCI animals' muscle synergy patterns were distinguished from each other and from the intacts'. Although sharing a lot of similarity, compared to the adult SCI animals, neonatal SCI animals had less synergies merging. Some xiv individual synergies of the neonatal SCIs' might resemble the intact animals more than adult SCIs'. To test the hypothesis, we examined the muscle synergy pattern using locomotor electromyography (EMG) in adult animals injured as neonates (T9/10 complete SCI, n=9), intact adult rats (n=12) and the same adult rats 10~14 days after T9/10 complete SCI (n=9). We found that adult SCI animals' synergies tended to merge post injury compared to the intact animals. The intacts also deviated from the neonatal and adult SCI animals regarding the correlation of all the synergies and individual synergy to a common synergy template. While sharing some similarity, in some individual synergies' correlation values to the common template, the neonatal animals were more similar to the adult SCIs shortly after injury than to the intacts. The neonatal synergies appeared to be preserved into adulthood and revealed after adult SCI. If given systematical training, would the synergies of adult SCI animals change with function? And if they do, would the change be the same regardless of the rehabilitation paradigms and recovery outcome? In order to answer these questions, we studied the synergy changes following robot-driven epidural stimulation combined with treadmill training (ES) and robotic assisted treadmill only (TM) systematic long-term training and we compared these to the animals resting in the cage after complete adult SCI. We hypothesized that synergies would tend to merge right after injury. As time went by after injury, the synergies' spatial structure would be simplified. However, with successful rehabilitation, the further merging and simplification of the synergies were avoided. To investigate the only (TM) systematic long-term training and we compared these to the animals resting in the cage after complete adult SCI. We hypothesized that synergies would tend to merge right after injury. As time went by after injury, the synergies' spatial structure would be simplified. However, with successful rehabilitation, the further merging and simplification of the synergies were avoided. To investigate the synergies' relationship to therapeutic methods and efficacy, we trained three groups of animals with ES training, TM training and in cage resting respectively. We examined their synergies through 8 weeks' rehabilitation period. ES and TM training showed beneficial effects on recovery after SCI. Synergy changes were linked with functional locomotion recovery. Unlike cage resting, the effective training harnessed and separated the synergies merging post injury and each synergy ended with more refined spatial patterns. However, although both ES and TM helped SCI animals recovered successfully, their underlying neural mechanisms were not the same in terms of synergy changes. Our study suggested that the TM training likely did not reverse the merging process to the extent that the ES training did.

This study investigated the effect of spinal cord injury (SCI) on nonlinear complexity of skin blood flow oscillations (BFO). Complexity of the characteristic frequencies embedded in BFO was described by the scaling coefficient derived by detrended fluctuation analysis (DFA) and the range of scaling coefficients derived from multifractal detrended fluctuation analysis (MDFA) in specific scale intervals. 23 subjects were recruited into this study, including 11 people with SCI and 12 healthy controls. Local heating-induced maximal sacral skin blood flow was measured by laser Doppler flowmetry. The results showed that metabolic BFO (0.0095-0.02 Hz) exhibited significantly lower complexity in people with SCI as compared with healthy controls (p<0.01) during maximal vasodilation. This study demonstrated that complexity analysis of BFO can provide information of blood flow dynamics beyond traditional spectral analysis.

In this study, a novel automatic method for segmenting muscle groups and adipose tissue in thigh MRI volumes is developed to quantify the negative effects of spinal cord injury (SCI) on fat and muscle distribution in individuals with severe SCI. The thigh volumes were segmented based on subcutaneous fat, inter-muscular fat and muscle tissue using Linear Combination of Discrete Gaussians algorithm. Furthermore, the three main compartments of the muscle tissue: knee extensor, knee flexor and hip adductor muscles were segmented utilizing the Joint Markov Gibbs Random Field (MGRF) model that integrates first order appearance model of the muscles, spatial information, and shape model to localize the muscle groups. The method was tested on 10 SCI and 10 non-disabled (ND) subjects and the results has shown high accuracy of 96.86 ± 3.48 for fat segmentation and 94.76 ± 1.70 for muscle group segmentation based on Dice similarity percentage. Next, we calculated 3 ratios based on the volumes of the subcutaneous fat to muscle tissue, inter-muscular fat to muscle and extensor to flexor for all subjects. Mann-Whitney statistical test showed that inter-muscular fat to muscle ratio was significantly greater in SCI than in ND group (p = 0.001).

Immune Regulatory Mechanisms Influence Early Pathology in Spinal Cord Injury and in Spontaneous Autoimmune Encephalomyelitis

To assess the effects of spinal cord injury (SCI) on perceived health-related quality of life (QOL). SCI is physically disabling, socially handicapping, and romantically limiting. Nevertheless, little is known about post-SCI neurocognitive and psychosocial life. Better understanding of the cognitive and emotional worlds of SCI patients is essential to better address and meet their needs and expectations. Twenty subjects with high-cord (T6 and above) complete (American Spinal Injury Association [ASIA] A) SCI (High SCI) were compared with 10 subjects with low-cord (T7 and below) ASIA A SCI (Low SCI) and with 11 Able-Bodied control subjects. Satisfaction with Life and Short Form-36 instruments were used to assess physical and emotional aspects of QOL. Analyses of variance were used to assess potential differences across groups. Overall, satisfaction with life was the same among the groups. Expectedly, High SCI and Low SCI subjects reported lower physical functioning than Able-Bodied subjects (p < 0.0001). But, oddly, there were no differences in perceived physical role, physical health, or social functioning. Furthermore, High SCI subjects reported better perceived mental health than Able-Bodied control subjects (p = 0.004) and a trend over Low SCI subjects (p = 0.06), better perceived emotional role in society (p = 0.02), and greater vitality (p = 0.01) than Low SCI subjects and Able-Bodied subjects. Despite severe physical impairment and disability and frequent medical complications, subjects with complete spinal cord injury at high anatomic levels report better than average quality of life, being overall content. Reasons for these findings are unclear. Psychological adaptive reactions are likely, but the possible role of physiologic and neurocognitive changes needs further exploration.

Following Spinal Cord Injury (SCI), 53% of people develop neuropathic pain (NP). NP can be more debilitating than other consequences of SCI, and a persistent health issue. Pharmacotherapies are commonly recommended for NP management in SCI, although severe pain often remains refractory to these treatments in many sufferers. Furthermore, poor medication adherence exists, stemming from unacceptable side-effects and fear of dependency.Sensorimotor stimulation using active walking with robotic assistance has not been well studied in NP after SCI, despite convincing locomotor-based pre-clinical studies, identifying prevention and reversal of NP.Our primary aim is to assess the impact of exoskeleton-based walking on NP intensity and interference after SCI and examine feasibility outcomes for progression to a definitive trial. This is a phase 2 single-blinded, randomised feasibility study. It will test the feasibility and acceptability of exoskeleton-based walking 3 times per week for 12 weeks (intervention), as a mechanistic-based intervention for NP after SCI. The comparator will be an equally dosed, blended relaxation programme devoid of motor imagery prompts. 40 participants with moderate-to-severe NP post SCI will be recruited and randomised to intervention and comparator groups.The primary outcomes are feasibility outcomes for progression to definitive trial which include recruitment and retention rates, adverse events and acceptability of the intervention.Secondary outcomes explore changes in NP intensity and interference as measured by the International Spinal Cord Injury Pain Basic Data Set 3.0 (ISCIPBDS) at baseline, post-intervention (week 13) and at 6-month follow-up. There is a need to explore non-pharmacological management of NP after SCI. The findings of this feasibility trial will inform the development of a future multicentre, international RCT. NCT06463418, 08/07/2024, https://clinicaltrials.gov/study/NCT06463418.

ObjectiveTo test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI.MethodsApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC’s) were analyzed.ResultsAD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC’s interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC’s by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p’s <0.05).ConclusionsSCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC’s IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

In an effort to understand the mechanisms involved in dysesthetic pain syndrome (DPS) in spinal cord injury (SCI) patients, four groups of 13 subjects each--SCI subjects with DPS, SCI subjects without pain, chronic low back pain subjects, and control subjects--were examined for sensory detection and pain thresholds at forearm, neck, and rostral trunk areas. Results indicated that the SCI pain group had significantly lower pain thresholds at all skin sites, compared to the SCI no-pain and chronic low back pain groups, and at the rostral trunk skin site, compared to the control group. The SCI pain group also showed a lower sensory detection threshold at the rostral trunk skin site than did the SCI no-pain group. Equally important, the SCI no-pain group had detection and pain thresholds significantly higher than those of the control group. The results suggest fundamental differences in somatosensory processing when DPS is or is not a consequence of SCI.

<p style="text-align: justify;"><span style="font-family: "times new roman";">Spinal cord injury is a common multiple disease, belongs to the central nervous injury disease, this kind of disease will be extremely destructive to the human body, has a high disability rate, has a serious impact on the quality of life of patients. Therefore, it is of great significance to explore the scientific treatment of spinal cord injury and promote the continuous improvement of treatment effect. The purpose of this paper is to explore the effect of oscillating electric field on the recovery of motor function and axon regeneration in gray rabbits with spinal cord injury, so as to provide theoretical support for the clinical treatment of spinal cord injury and promote the continuous improvement of the actual therapeutic effect of spinal cord injury. Firstly, the concept, pathological development and main manifestations of spinal cord injury were discussed in detail, and then the common treatment methods of spinal cord injury were introduced. Then, the influence of oscillating electric field on motor function recovery and axon regeneration of gray rabbits with spinal cord injury was investigated through the establishment of spinal cord injury model. The experimental results showed that compared with no interference electric field, the motor function and axonal regeneration ability of gray rabbits with spinal cord injury under the intervention of oscillating electric field were significantly improved, with about 19% increase in axonal regeneration ability, about 19% increase in injury recovery speed, and about 17% increase in overall recovery effect. In summary, the oscillating electric field can promote the effective recovery of spinal cord motor function in gray rabbits with spinal cord injury, but the intervention time of oscillating electric field should last more than 6 weeks.</span>

Chronic hypoxia causes morphological alterations in astroglia in the phrenic nucleus of young adult rats

Current developments in spinal cord injury research

The spinal cord facilitates communication between the brain and the body, containing intrinsic systems that work with lower motor neurons (LMNs) to manage movement. Spinal cord injuries (SCIs) can lead to partial paralysis and dysfunctions in muscles below the injury. While traditionally this paralysis has been attributed to disruptions in the corticospinal tract, a growing body of work demonstrates LMN damage is a factor. Motor units, comprising the LMN and the muscle fibers with which they connect, are essential for voluntary movement. Our understanding of their changes post-SCI is still emerging, but the health of motor units is vital, especially when considering innovative SCI treatments like nerve transfer surgery. This review seeks to collate current literature on how SCI impact motor units and explore neuromuscular clinical implications and treatment avenues. SCI reduced motor unit number estimates, and surviving motor units had impaired signal transmission at the neuromuscular junction, force-generating capacity, and excitability, which have the potential to recover chronically, yet the underlaying mechanisms are unclear. Furthermore, electrodiagnostic evaluations can aid in assessing the health lower and upper motor neurons, identify suitable targets for nerve transfer surgeries, and detect patients with time sensitive injuries. Lastly, many electrodiagnostic abnormalities occur in both chronic and acute SCI, yet factors contributing to these abnormalities are unknown. Future studies are required to determine how motor units adapt following SCI and the clinical implications of these adaptations.