Neuronal repair after spinal cord injury by in vivo astrocyte reprogramming mediated by the overexpression of NeuroD1 and Neurogenin-2.

BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.

Repetitive Transcranial Magnetic Stimulation with Body Weight-supported Treadmill Training Enhances Independent Walking of Individuals with Chronic Incomplete Spinal Cord Injury: A Pilot Randomized Clinical Trial.

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with body weight-support treadmill training (BWSTT) for improving walking function of individuals with chronic incomplete spinal cord injury (iSCI). A 4-week, double-blinded, randomized, sham-controlled pilot study involved 12 sessions of real (10 Hz, 1800 pulses) or sham rTMS combined with BWSTT (15-20 min, moderate intensity). Walking independence was assessed using the Walking Index for Spinal Cord Injury II (WISCI-II). Lower extremity motor function (lower extremity motor score [LEMS]) and spasticity, sensory function, functional independence (Spinal Cord Injury Measure III [SCIM-III]), and quality of life were also assessed. Walking independence (WISCI-II) after the 6th session was higher in the BWSTT/rTMS real (n = 7) (median change (IQR): 3 (1.5 to 3.5)) than in the sham group (n = 8) (median change (IQR): 0 (0 to 0.25), but there was no difference between groups after 12th session (BWSTT/rTMS real median change (IQR): 4 (2 to 5); BWSSTT/rTMS sham median change (IQR): 0 (0 to 3.25). Compared to baseline, LEMS and SCIM-III mobility scores were increased after 12 sessions in the BWSTT/rTMS real but not in the sham group. Within- and between-group sensory function, functional independence, and quality of life remained similar. This preliminary result suggests that combining BWSTT with rTMS could lead to earlier gait improvement in patients with chronic iSCI.

Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury.

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin-eosin) and immunohistochemistry for NeuN, ß-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for ß-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in ß-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.

Trans-spinal magnetic stimulation combined with kinesiotherapy as a new method for enhancing functional recovery in patients with spinal cord injury due to neuromyelitis optica: a case report.

BACKGROUND: Experimental studies have shown that repetitive trans-spinal magnetic stimulation (TsMS) decreases demyelination and enables recovery after spinal cord injury (SCI). However, the usefulness of TsMS in humans with SCI remains unclear. Therefore, the main objective of this study is to evaluate the effects of TsMS combined with kinesiotherapy on SCI symptoms. We describe a protocol treatment with TsMS and kinesiotherapy in a patient with SCI due to neuromyelitis optica (NMO)-associated transverse myelitis. CASE PRESENTATION: A 23-year-old white male with NMO spectrum disorders started symptoms in 2014 and included lumbar pain evolving into a mild loss of strength and sensitivity in both lower limbs. Five months later, the symptoms improved spontaneously, and there were no sensorimotor deficits. Two years later, in 2016, the symptoms recurred with a total loss of strength and sensitivity in both lower limbs. Initially, physiotherapy was provided in 15 sessions with goals of motor-sensory recovery and improving balance and functional mobility. Subsequently, TsMS (10 Hz, 600 pulses, 20-seconds inter-trains interval, at 90% of resting motor threshold of the paravertebral muscle) was applied at the 10th thoracic vertebral spinous process before physiotherapy in 12 sessions. Outcomes were assessed at three time points: prior to physiotherapy alone (T-1), before the first session of TsMS combined with kinesiotherapy (T0), and after 12 sessions of TsMS combined with kinesiotherapy (T1). The patient showed a 25% improvement in walking independence, a 125% improvement in balance, and an 18.8% improvement in functional mobility. The Patient Global Impression of Change Scale assessed the patient's global impression of change as 'much improved'. CONCLUSION: TsMS combined with kinesiotherapy may safely and effectively improve balance, walking independence, and functional mobility of patients with SCI due to NMO-associated transverse myelitis.

Activity-based locomotor training: improving the movement in children with spinal cord injury.

OBJECTIVE: The objective of this study was to investigate the effects of activity-based locomotor training (ABLT) on motor function and walking ability in children with spinal cord injury (SCI). MATERIALS AND METHODS: The Chinese National Knowledge Infrastructure, WanFang, VIP, PubMed, and Web of Science databases were searched for related studies, with two reviewers subsequently evaluating the literature quality using the Cochrane Handbook. RESULTS: A total of 11 studies were eligible, while only one met the ABLT standard program criteria. Overall, ABLT significantly improved the lower limb motor function, increased walking speed and distance, and improved the daily living ability of children with SCI. CONCLUSIONS: The ABLT strategy is of great significance to the motor function and walking ability of children with SCI. At present, there exist few studies on the application of ABLT for pediatric SCI. Further control studies with a larger sample size are required to improve the ABLT program guidelines for children with SCI.

OBJETIVO: Discuta el impacto del entrenamiento ejercicio basado en la actividad en la lesión de la médula espinal en la función de movimiento de los niños y la capacidad de caminar. MATERIALS Y MÉTODOS: Según China Zhiwang, Wanfang, VIP, PubMed, Science Network y otros documentos relacionados como fuente de datos. Dos revisores usan calidad de evaluación manual de Cochrane. RESULTADOS: Un total de 11 estudios cumplen con las condiciones. Solo hay un estudio que cumple con los proyectos estándar de ABLT. General, ABLT mejora significativamente la función de los niños con lesiones de la médula espinal, aumenta la velocidad y la distancia de caminar y mejora la capacidad de la vida diaria. CONCLUSIÓN: La estrategia ABLT es de gran importancia para la función de movimiento de los niños de la médula espinal y la capacidad de caminar. En la actualidad, ABLT tiene menos investigación en lesión pediátrica de la médula espinal. Es necesario mostrar la cantidad de muestra y controlar la investigación para mejorar las pautas del plan ABLT para el daño de la médula espinal a los niños.

The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration.

Tissue engineering for spinal cord injury (SCI) remains a complex and challenging task. Biomaterial scaffolds have been suggested as a potential solution for supporting cell survival and differentiation at the injury site. However, different biomaterials display multiple properties that significantly impact neural tissue at a cellular level. Here, we evaluated the behavior of different cell lines seeded on chitosan (CHI), poly (ε-caprolactone) (PCL), and poly (L-lactic acid) (PLLA) scaffolds. We demonstrated that the surface properties of a material play a crucial role in cell morphology and differentiation. While the direct contact of a polymer with the cells did not cause cytotoxicity or inhibit the spread of neural progenitor cells derived from neurospheres (NPCdn), neonatal rat spinal cord cells (SCC) and NPCdn only attached and matured on PCL and PLLA surfaces. Scanning electron microscopy and computational analysis suggested that cells attached to the material's surface emerged into distinct morphological populations. Flow cytometry revealed a higher differentiation of neural progenitor cells derived from human induced pluripotent stem cells (hiPSC-NPC) into glial cells on all biomaterials. Immunofluorescence assays demonstrated that PCL and PLLA guided neuronal differentiation and network development in SCC. Our data emphasize the importance of selecting appropriate biomaterials for tissue engineering in SCI treatment.

Effects of exercise training on neurological recovery, TGF-ß1, HIF-1α, and Nogo-NgR signaling pathways after spinal cord injury in rats.

OBJECTIVE: To evaluate the effects of exercise training on neurological recovery, Growth Transforming Factor-ß1 (TGF-ß1), Hypoxia Inducible Factor-1α (HIF-1α), and Nogo-NgR signaling pathways after spinal cord injury in rats. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: normal group, sham-operated group, model group, and training group. The rat spinal cord injury model was established using Allen's method, and the training group received exercise training on the 8th day postoperatively. The Basso, Beattie and Bresnahan (BBB) score, modified Tarlow score, and inclined plane test scores were compared in each group before injury and 1, 7, 14, 21 and 28 days after injury. RESULTS: The BBB score and modified Tarlow score of the model group and the training group were 0 at the first day after the injury, and gradually increased on the seventh day onwards (p < 0.05). The BBB score and modified Tarlow score of the training group were higher than those of the model group at the 14th, 21st and 28th day (p < 0.05). The angles of the inclined plate at multiple time points after injury were lower in the model group and the training group than in the normal group and the sham-operated group (p < 0.05); The angles of the inclined plate at the 14th, 21st and 28th day after injury were higher in the training group than in the model group (p < 0.05). CONCLUSION: The mechanism of exercise training may be connected to the inhibition of the Nogo-NgR signaling pathway to promote neuronal growth.

Inspiratory muscle training on quality of life in individuals with spinal cord injury: A systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The objective was to summarize the effectiveness of Inspiratory Muscle Training (IMT) on the quality of life in individuals with Spinal Cord Injury (SCI). METHODS: An online systematic literature search was conducted in the following databases: PubMed/MEDLINE, PubMed CENTRAL, EMBASE, ISI Web of Science, SciELO, CINAHL/SPORTDiscus, and PsycINFO. Randomized and non-randomized clinical studies investigating the effectiveness of IMT in quality of life were included in the present study. The results used the mean difference and 95% confidence interval for maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), maximal expiratory pressure (MEP), and the standardized mean differences for the quality of life and maximum ventilation volume. RESULTS: The search found 232 papers, and after the screening, four studies met the inclusion criteria and were included in the meta-analytical procedures (n = 150 participants). No changes were demonstrated in the quality of life domains (general health, physical function, mental health, vitality, social function, emotional problem, and pain) after IMT. The IMT provided a considerable effect over the MIP but not on FEV1 and MEP. Conversely, it was not able to provide changes in any of the quality of life domains. None of the included studies evaluated the IMT effects on the expiratory muscle maximal expiratory pressure. CONCLUSION: Evidence from studies shows that inspiratory muscle training improves the MIP; however, this effect does not seem to translate to any change in the quality of life or respiratory function outcomes in individuals with SCI.

Treatment of Acute Spinal Cord Injuries: A Survey Among Iberolatinoamerican Spine Surgeons - Part 2 Timing to Surgery / Tratamento de lesões agudas da medula espinal: Uma pesquisa entre cirurgiões de coluna iberoamericanos - Parte 2: Momento da cirurgia

Abstract Objective The objective of the present study was to evaluate the current practice in terms of timing to surgery in acute spinal cord injury (ASCI) patients among spinal surgeons from Iberolatinoamerican countries. Methods A descriptive cross-sectional study design as a questionnaire was sent by an email for all members of the Sociedad Ibero Latinoamericana de Columna (SILACO, in the Spanish acronym) and associated societies. Results A total of 162 surgeons answered questions related to the timing for surgery. Sixty-eight (42.0%) considered that ASCI with complete neurology injury should be treated within 12 hours, 54(33.3%) performed early decompression within 24 hours, and 40 (24,7%) until the first 48 hours. Regarding ASCI with incomplete neurological injury, 115 (71.0%) would operate in the first 12 hours. There was a significant difference in the proportion of surgeons that would operate ASCI within ≤ 24 hours, regarding the type of injury (complete injury:122 versus incomplete injury:155; p<0.01). In the case of patients with central cord syndrome without radiological evidence of instability, 152 surgeons (93.8%) would perform surgical decompression: 1 (0.6%) in the first 12 hours, 63 (38.9%) in 24 hours, 4 (2.5%) in 48 hours, 66 (40.7%) in the initial hospital stay, and 18 (11.1%) after neurologic stabilization. Conclusion All inquired surgeons favour early decompression, with the majority performing surgery in the first 24 hours. Decompression is performed earlier in cases of incomplete than in complete injuries. In cases of central cord syndrome without radiological evidence of instability, there is a tendency towards early surgical decompression, but the timing is still extremely variable. Future studies are needed to identify the ideal timing for decompression of this subset of ASCI patients.

Resumo Objetivo O objetivo do presente estudo foi avaliar a prática atual em termos de momento de realização da cirurgia em pacientes com lesão medularaguda (LMA) entre cirurgiões de coluna de países ibero-americanos. Métodos Estudo transversal descritivo com base em um questionário enviado por correio eletrônico para todos os membros da Sociedad Ibero Latinoamericana de Columna (SILACO, na sigla em espanhol) e sociedades associadas. Resultados Um total de 162 cirurgiões responderam a perguntas relacionadas ao momento da cirurgia. Sessenta e oito (42,0%) consideraram que a LMA com lesão neurológica completa deve ser tratada em até 12 horas, 54 (33,3%) realizariam a descompressão precoce em até 24 horas e 40 (24,7%) fariam este procedimento nas primeiras 48 horas. Em relação à LMA com lesão neurológica incompleta, 115 (71,0%) operariam nas primeiras 12 horas. Houve diferença significativa na proporção de cirurgiões que fariam o tratamento cirúrgico da LMA em ≤ 24 horas quanto ao tipo de lesão (lesão completa [122] versus lesão incompleta [155]; p<0.01). Em pacientes com síndrome medular central sem evidência radiológica de instabilidade, 152 cirurgiões (93,8%) realizariam a descompressão cirúrgica: 1 (0,6%) nas primeiras 12 horas, 63 (38,9%) em 24 horas, 4 (2,5%) em 48 horas, 66 (40,7%) no internamento inicial e 18 (11,1%) após a estabilização neurológica. Conclusão Todos os cirurgiões participantes favoreceram a descompressão precoce; a grande maioria realizaria a cirurgia nas primeiras 24 horas. A descompressão é feita antes em casos de lesões incompletas do que em lesões completas. Nos casos de síndrome medular central sem evidência radiológica de instabilidade, há uma tendência à descompressão cirúrgica precoce, mas o momento de intervenção ainda é extremamente variável. Estudos futuros são necessários para identificar o momento ideal para descompressão neste subconjunto de pacientes com LMA.

Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats.

Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFß) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury.

Low-intensity pulsed ultrasound partially reversed the deleterious effects of a severe spinal cord injury-induced bone loss and osteoporotic fracture healing in paraplegic rats.

PURPOSE: To evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on the quality of femoral fracture callus formation in rats with severe osteoporosis secondary to spinal cord injury (SCI). METHODS: Forty-five male rats were equally divided into three groups: the Sham group underwent sham surgery for SCI followed by surgery for femoral fracture on day ten post-spine surgery; the SCI group sustained a complete transection of the spinal cord and a femoral fracture ten days post-SCI; and the SCI group treated with ultrasound (SCI + US), which also sustained a femoral fracture on day ten post-SCI, concomitant with daily application of LIPUS at the fracture site. RESULTS: At the non-fractured tibias, LIPUS counteracted the SCI-induced bone loss by normalizing the osteoblastic-related gene expression, decreasing resorptive area, increasing trabecular area, and decreasing RANK and RANK-L-positive areas, which resulted in higher cortical volume and stronger tibias. Likewise, LIPUS was effective at restoring bone fracture healing in SCI rats; by promoting endochondral ossification, increasing collagen deposition and OPG-positive-area, decreasing resorptive area, which led to higher density and improved microarchitecture, ultimately resulting in stronger fracture callus. CONCLUSION: At the tibias, LIPUS counteracted the SCI-induced bone loss effects by simultaneously increasing bone formation and decreasing bone resorption. We also evidenced the osteogenic effects of LIPUS at partially restoring the endochondral ossification during callus formation, leading to a newly formed tissue with improved microarchitecture and mechanical integrity. Therefore, LIPUS may be an efficient and non-invasive approach to prevent bone loss and osteoporotic fracture in SCI individuals.

Training with noninvasive brain-machine interface, tactile feedback, and locomotion to enhance neurological recovery in individuals with complete paraplegia: a randomized pilot study.

In recent years, our group and others have reported multiple cases of consistent neurological recovery in people with spinal cord injury (SCI) following a protocol that integrates locomotion training with brain machine interfaces (BMI). The primary objective of this pilot study was to compare the neurological outcomes (motor, tactile, nociception, proprioception, and vibration) in both an intensive assisted locomotion training (LOC) and a neurorehabilitation protocol integrating assisted locomotion with a noninvasive brain-machine interface (L + BMI), virtual reality, and tactile feedback. We also investigated whether individuals with chronic-complete SCI could learn to perform leg motor imagery. We ran a parallel two-arm randomized pilot study; the experiments took place in São Paulo, Brazil. Eight adults sensorimotor-complete (AIS A) (all male) with chronic (> 6 months) traumatic spinal SCI participated in the protocol that was organized in two blocks of 14 weeks of training and an 8-week follow-up. The participants were allocated to either the LOC group (n = 4) or L + BMI group (n = 4) using block randomization (blinded outcome assessment). We show three important results: (i) locomotion training alone can induce some level of neurological recovery in sensorimotor-complete SCI, and (ii) the recovery rate is enhanced when such locomotion training is associated with BMI and tactile feedback (∆Mean Lower Extremity Motor score improvement for LOC = + 2.5, L + B = + 3.5; ∆Pinprick score: LOC = + 3.75, L + B = + 4.75 and ∆Tactile score LOC = + 4.75, L + B = + 9.5). (iii) Furthermore, we report that the BMI classifier accuracy was significantly above the chance level for all participants in L + B group. Our study shows potential for sensory and motor improvement in individuals with chronic complete SCI following a protocol with BMIs and locomotion therapy. We report no dropouts nor adverse events in both subgroups participating in the study, opening the possibility for a more definitive clinical trial with a larger cohort of people with SCI.Trial registration: http://www.ensaiosclinicos.gov.br/ identifier RBR-2pb8gq.

Physiological parameters and the use of compression stockings in individuals with spinal cord injuries: a scoping review.

STUDY DESIGN: Scoping review. OBJECTIVE: To summarize information on the physiological effects of compression stockings (CS) in individuals with spinal cord injuries (SCI) and suggest areas for future research. METHODS: We asked, "What are the physiological effects of CS use in individuals with SCI?" Original studies of patients with SCI regardless of sex and age that focused on SCI and CS were included. Five biomedical databases were searched. Studies were selected by three researchers in two stages, starting with an abstract and title screening and continuing with a full text review for application of the inclusion and exclusion criteria. A narrative synthesis was then performed. RESULTS: An initial search yielded 283 titles, of which five met the inclusion criteria and were subjected to the full text review. Among them, there were 78 individuals with SCI. The studies found that the use of CS at rest reduced deep vein thrombosis (DVT) and vascular capacitance but increased systolic blood pressure and norepinephrine level., three studies tested the use of CS During exercise; one found that time of the last lap in a standard court test was negatively affected; however, the greatest benefits were observed after exercises, such as reduced blood lactate level, improved autonomic function, and increased blood flow to the upper limbs. CONCLUSION: We conclude that future research should examine the physiological effects and relationship of CS with: (a) pharmacological interventions, (b) body position changes, (c) physical fitness level, (d) wheelchair use duration, (e) exercise-induced thermal stress, (f) thermal stress mitigation, and (g) edema reduction.

Raman spectroscopy of healthy, injured and amniotic membrane treated rat spinal cords.

Spinal cord injury is a significant public health issue with high psychological and financial costs to both the family and the society. Effective treatment strategies are hence of immense value. Several reports have suggested application of amniotic membrane for treating injuries, and there is evidence that it may be used to treat spinal injuries. In this animal model study, we explore biochemical changes in amniotic membrane treated injured spinal cord with respect to untreated injured and uninjured spinal cord using Raman spectroscopy. Multivariate statistical analysis is able to classify control, untreated, and treated with 92%, 87%, and 80% efficiency, respectively; suggesting unique biochemical changes in each group. Such studies may lead to development of minimally invasive methodologies for spinal cord injury treatment monitoring.

Effects of functional electro-stimulation combined with blood flow restriction in affected muscles by spinal cord injury.

Muscle atrophy is a great consequence of spinal cord injuries (SCI) due to immobility. SCI's detrimental effects on large muscle groups may lead to secondary effects such as glucose intolerance, increased risk of metabolic syndrome, and diabetes. Exercising with blood flow restriction (BFR) has been proposed as an effective method to induce hypertrophy using low training loads, with little or no muscle damage. This study investigated acute and chronic effects of low-intensity functional electrical stimulation (FES) combined with BFR on muscles affected by spinal cord injury. The acute effects of one bout of FES with (FES + BFR group) and without BFR (FES group) on muscle thickness (MT) and edema formation were compared. The chronic effects on MT and edema following 8 weeks of twice weekly training with and without BFR were also compared. The FES + BFR group showed MT and edema increases compared to the FES only group (p< 0.05). The FES + BFR showed a chronic MT increase after 4 weeks of training (p <0.05), with no further MT increases from the 4th to the 8th week (p>0.05). Following 3 weeks of detraining, MT decreased to baseline. No MT changes were observed in the FES (p>0.05). The FES + BF stimuli induced MT increases on the paralyzed skeletal muscles of SCI. The acute effects suggest that FES causes a greater metabolite accumulation and edema when combined with BFR. The early increases in MT can be attributed to edema, whereas after the 4th week, it is likely to be related to muscle hypertrophy. Register Clinical Trial Number on ReBeC: RBR-386rm8.

Management of Acute Subaxial Trauma and Spinal Cord Injury in Professional Collision Athletes.

Sports-related acute cervical trauma and spinal cord injury (SCI) represent a rare but devastating potential complication of collision sport injuries. Currently, there is debate on appropriate management protocols and return-to-play guidelines in professional collision athletes following cervical trauma. While cervical muscle strains and sprains are among the most common injuries sustained by collision athletes, the life-changing effects of severe neurological sequelae (ie, quadriplegia and paraplegia) from fractures and SCIs require increased attention and care. Appropriate on-field management and subsequent transfer/workup at an experienced trauma/SCI center is necessary for optimal patient care, prevention of injury exacerbation, and improvement in outcomes. This review discusses the epidemiology, pathophysiology, clinical presentation, immediate/long-term management, and current return-to-play recommendations of athletes who suffer cervical trauma and SCI.

The efficacy of immediate implantation of macroporous poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel after laceration spinal cord injury in young rats / Eficacia de la implantación inmediata de hidrogel macroporoso de poli (N- [2-hidroxipropil] - metacrilamida) después de una lesión de la médula espinal en ratas jóvenes

SUMMARY: Spinal cord regeneration after mechanical injury is one of the most difficult biomedical problems. This article evaluates the effect of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel (PHPMA-hydrogel) on spinal cord regeneration in young rats after lateral spinal cord hemi-excision (laceration) at the level of segments T12-T13 (TrGel group). The locomotor function score (FS) and the paretic hindlimb spasticity score (SS) were assessed according to Basso-Beattie-Bresnahan (BBB) and Ashworth scales, respectively, and compared to a group of animals with no matrix implanted (Tr group). Regeneration of nerve fibers at the level of injury was evaluated at ~5 months after spinal cord injury (SCI). One week after the SCI induction, the FS on the BBB scale was 0.9±0.5 points in the Tr group and 3.6±1.2 points in the TrGel group. In the Tr group, the FS in 5 months was significantly lower than in 2 weeks after SCI, while no significant changes in FS were detected in the TrGel group over the entire observation period. The final FS was 0.8±0.3 points in the Tr group and 4.5±1.8 points in the TrGel group. No significant changes in SS have been observed in the TrGel group throughout the experiment, while the Tr group showed significant increases in SS at 2nd week, 6th week, 3th month and 5th month. The SS in 5 months was 3.6±0.3 points on the Ashworth scale in the Tr group and 1.8±0.7 points in the TrGel group. Throughout the observation period, significant differences in FS between groups were observed only in 5 weeks after SCI, whereas significant differences in SS were observed in 2, 3 and 6-8 weeks post-injury. Glial fibrous tissue containing newly formed nerve fibers, isolated or grouped in small clusters, that originated from the surrounding spinal cord matter have been found between the implanted hydrogel fragments. In conclusion, PHPMA-hydrogel improves recovery of the hindlimb locomotor function and promotes regenerative growth of nerve fibers. Further research is needed to clarify the mechanism of this PHPMA-hydrogel effect.

RESUMEN: La regeneración de la médula espinal después de una lesión mecánica es uno de los problemas biomédicos más difíciles. Este artículo evalúa el efecto del hidrogel de poli (N- [2-hidroxipropil] -metacrilamida) (PHPMA-hidrogel) sobre la regeneración de la médula espinal en ratas jóvenes después de la hemiescisión lateral de la médula espinal (lesión) a nivel de los segmentos T12 - T13 (Grupo TrGel). La puntuación de la función locomotora (FS) y la puntuación de espasticidad parética de las patas traseras (SS) se evaluaron de acuerdo con las escalas de Basso- Beattie-Bresnahan (BBB) y Ashworth, respectivamente, y se compararon con un grupo de animales sin matriz implantada (grupo Tr). Se evaluó la regeneración de las fibras nerviosas al nivel de la lesión ~ 5 meses después de la lesión de la médula espinal (LME). Una semana después de la inducción de SCI, el FS en la escala BBB fue 0,9 ± 0,5 puntos en el grupo Tr y 3,6 ± 1,2 puntos en el grupo TrGel. En el grupo Tr, el FS en 5 meses fue significativamente menor que en 2 semanas después de SCI, mientras que no se detectaron cambios significativos en FS en el grupo TrGel durante el período de observación. El FS final fue de 0,8 ± 0,3 puntos en el grupo Tr y de 4,5 ± 1,8 puntos en el grupo TrGel. No se han obser- vado cambios significativos en SS en el grupo TrGel durante el experimento, mientras que el grupo Tr mostró aumentos significativos en SS en la 2ª semana, 6ª semana, 3º mes y 5º mes. La SS en 5 meses fue de 3,6 ± 0,3 puntos en la escala de Ashworth en el grupo Tr y de 1,8 ± 0,7 puntos en el grupo TrGel. A lo largo del período de observación, se observaron diferencias significativas en FS entre los grupos solo en 5 semanas después de la LME, mientras que se observaron diferencias significativas en SS en 2, 3 y 6-8 semanas después de la lesión. Entre los fragmentos de hidrogel implantados se observó tejido fibroso glial que contenía fibras nerviosas recién formadas, aisladas o agrupadas en pequeños grupos, que se originaban a partir de la materia de la médula espinal circundante. En conclusión, PHPMA-hydrogel mejora la recuperación de la función locomotora de las patas traseras y promueve el crecimiento regenerativo de las fibras nerviosas. Se requieren más estudios para aclarar el mecanismo del efecto de hidrogel PHPMA.

Immunomodulation induced by central nervous system-related peptides as a therapeutic strategy for neurodegenerative disorders.

Neurodegenerative diseases (NDD) are disorders characterized by the progressive loss of neurons affecting motor, sensory, and/or cognitive functions. The incidence of these diseases is increasing and has a great impact due to their high morbidity and mortality. Unfortunately, current therapeutic strategies only temporarily improve the patients' quality of life but are insufficient for completely alleviating the symptoms. An interaction between the immune system and the central nervous system (CNS) is widely associated with neuronal damage in NDD. Usually, immune cell infiltration has been identified with inflammation and is considered harmful to the injured CNS. However, the immune system has a crucial role in the protection and regeneration of the injured CNS. Nowadays, there is a consensus that deregulation of immune homeostasis may represent one of the key initial steps in NDD. Dr. Michal Schwartz originally conceived the concept of "protective autoimmunity" (PA) as a well-controlled peripheral inflammatory reaction after injury, essential for neuroprotection and regeneration. Several studies suggested that immunizing with a weaker version of the neural self-antigen would generate PA without degenerative autoimmunity. The development of CNS-related peptides with immunomodulatory neuroprotective effect led to important research to evaluate their use in chronic and acute NDD. In this review, we refer to the role of PA and the potential applications of active immunization as a therapeutic option for NDD treatment. In particular, we focus on the experimental and clinical promissory findings for CNS-related peptides with beneficial immunomodulatory effects.