Effect of aerobic exercise program on neuropathic pain and quality of life in person with paraplegia: study protocol for a randomized controlled trial.

BACKGROUND: Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. METHODOLOGY: This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks. OUTCOME MEASURES: International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. DISCUSSION: The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.

Inhibiting the NF-κB/DRP1 Axis Affords Neuroprotection after Spinal Cord Injury via Inhibiting Polarization of Pro-Inflammatory Microglia.

BACKGROUND: Spinal cord injury (SCI) is considered a central nervous system (CNS) disorder. Nuclear factor kappa B (NF-κB) regulates inflammatory responses in the CNS and is implicated in SCI pathogenesis. The mechanism(s) through which NF-κB contributes to the neuroinflammation observed during SCI however remains unclear. METHODS: SCI rat models were created using the weight drop method and separated into Sham, SCI and SCI+NF-κB inhibitor groups (n = 6 rats per-group). We used Hematoxylin-Eosin Staining (H&E) and Nissl staining for detecting histological changes in the spinal cord. Basso-Beattie-Bresnahan (BBB) behavioral scores were utilized for assessing functional locomotion recovery. Mouse BV2 microglia were exposed to lipopolysaccharide (LPS) to mimic SCI-induced microglial inflammation in vitro. RESULTS: Inhibition of NF-κB using JSH-23 alleviated inflammation and neuronal injury in SCI rats' spinal cords, leading to improved locomotion recovery (p < 0.05). NF-κB inhibition reduced expression levels of CD86, interleukin-6 (IL-6), IL-1ß, and inducible Nitric Oxide Synthase (iNOS), and improved expression levels of CD206, IL-4, and tissue growth factor-beta (TGF-ß) in both LPS-treated microglia and SCI rats' spinal cords (p < 0.05). Inhibition of NF-κB also effectively suppressed mitochondrial fission, evidenced by the reduced phosphorylation of dynamin-related protein 1 (DRP1) at Ser616 (p < 0.001). CONCLUSION: We show that inhibition of the NF-κB/DRP1 axis prevents mitochondrial fission and suppresses pro-inflammatory microglia polarization, promoting neurological recovery in SCI. Targeting the NF-κB/DRP1 axis therefore represents a novel approach for SCI.

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.

Kinematics-Based Predictions of External Loads during Handcycling.

The increased risk of cardiovascular disease in people with spinal cord injuries motivates work to identify exercise options that improve health outcomes without causing risk of musculoskeletal injury. Handcycling is an exercise mode that may be beneficial for wheelchair users, but further work is needed to establish appropriate guidelines and requires assessment of the external loads. The goal of this research was to predict the six-degree-of-freedom external loads during handcycling from data similar to those which can be measured from inertial measurement units (segment accelerations and velocities) using machine learning. Five neural network models and two ensemble models were compared against a statistical model. A temporal convolutional network (TCN) yielded the best predictions. Predictions of forces and moments in-plane with the crank were the most accurate (r = 0.95-0.97). The TCN model could predict external loads during activities of different intensities, making it viable for different exercise protocols. The ability to predict the loads associated with forward propulsion using wearable-type data enables the development of informed exercise guidelines.

Enhanced neural recovery and reduction of secondary damage in spinal cord injury through modulation of oxidative stress and neural response.

Spinal cord injury (SCI) presents a critical medical challenge, marked by substantial neural damage and persistent functional deficits. This study investigates the therapeutic potential of cold atmospheric plasma (CAP) for SCI, utilizing a tailored dielectric barrier discharge (DBD) device to conduct comprehensive in vivo and in vitro analyses. The findings show that CAP treatment significantly improves functional recovery after SCI, reduces neuronal apoptosis, lowers inflammation, and increases axonal regeneration. These findings illustrate the efficacy of CAP in fostering a conducive environment for recovery by modulating inflammatory responses, enhancing neuronal survival, and encouraging regenerative processes. The underlying mechanism involves CAP's reactive oxygen species (ROS) reduction, followed by activating antioxidant enzymes. These findings position CAP as a pioneering approach for spinal cord injury (SCI) treatment, presenting opportunities for improved neural recovery and establishing a new paradigm in SCI therapy.

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.

Bowel and Bladder Dysfunction after SCI: A Comparison between India and Canada.

Background: The inclusion of people living with spinal cord injury (SCI) in research has allowed for an informed understanding of priorities of recovery of which bowel dysfunction and bladder dysfunction have been continuously identified. Research has also demonstrated the global disparities in SCI outcomes particularly when comparing high- and low-income countries. Currently, there is a lack of direct comparison between countries when assessing SCI outcomes. Objectives: This is an exploratory study to better understand bowel and bladder dysfunction amongst individuals with SCI in India and Canada. Methods: Data from 33 participants were analyzed. Participants completed an online questionnaire assessing demographic information and the Neurogenic Bowel Dysfunction (NBD) score, Wexner score, Neurogenic Bladder Symptom Score (NBSS), and the Incontinence Quality of Life Instrument (I-QOL). Continuous data were compared using t tests. For not normally distributed data, the independent Mann-Whitney U test was used. Categorical variables were evaluated for association using Fisher's exact or chi-square test, depending on the sample size. Results: Independent Mann-Whitney U test demonstrated that the Canadian participants had poorer bowel function with higher total NBD scores (p = .007) and less frequent bowel movements (p = .036), and they were more likely to experience uneasiness, headaches, and perspiration during bowel movements (p < .001). NBSS results indicated a small but significantly higher proportion of the Indian participants were unsatisfied or unhappy with their bladder function (p = .049). The distribution of Wexner and I-QOL scores were the same across countries. Conclusion: Potential explanations for differences include lifestyle, management, financial resources, patient and caregiver education, and societal pressures, which are all heavily influenced by cultural, geographical, and economic circumstances.

Functional Sitting Balance and Anthropometric Measures Are Related to Inspiratory Muscle Performance in People with Spinal Cord Injury.

Background: Respiratory complications are a leading cause of mortality post spinal cord injury (SCI). Along with breathing, respiratory muscles have a role in maintaining seated balance. Postinjury breathing influences respiratory muscle function. Preliminary evidence indicates a relation between respiratory muscle function and seated balance in people with chronic SCI dwelling in the community, but the relationship between balance and body habitus has not been explored. Objectives: To explore the relationships among inspiratory muscle function, functional seated balance (FSB), and body habitus in people with SCI. Methods: A convenience sample of inpatients with SCI (C5-T12) aged 18 to 60 years who were using a wheelchair was recruited from November 2022 to March 2023. Those with additional neurological disorders or respiratory support were excluded. Respiratory muscle function measures included maximal inspiratory pressure (MIP), sustained MIP (SMIP), and Fatigue Index Test (FIT). FSB was scored using the Function in Sitting Test (FIST). Body habitus was assessed using the axillary: umbilical (A:U) ratio. Spearman correlations explored the relationships. Results: Thirty-eight of 42 screened participants were eligible and participated (male, 32). Levels of injury ranged from C5 to T12. The mean (SD) age and duration of injury of the sample was 25.61 (6.68) years and 31.03 (28.69) months, respectively. SMIP and FIT correlated significantly with FSB (r s= .441, p = .01, and r s= .434, p = .006, respectively). A significant correlation between SMIP and A:U ratio (r s= -.330, p = .043) was observed. Conclusion: We observed a significant correlation between inspiratory pressure parameters and both functional seated balance and body habitus, adding to evidence on postural role of respiratory muscles.

The Effect of 12 Weeks of Rebound Therapy Exercise Training on Walking Ability of Spinal Cord Injury Patients.

Background: Walking ability is a crucial factor for recovery and rehabilitation of spinal cord injury (SCI) patients. Objectives: The aim of this study was to investigate the effect of 12 weeks of rebound therapy on walking parameters in SCI patients. Methods: Thirty members of Isfahan Spinal Cord Injury Association participated in this experimental study using a convenience sampling method. This study was approved by the ethics committee of the University of Isfahan (IR.UI.REC.1400.118). The participants were randomly assigned to control and rebound groups using a matched randomization method. Data were collected before and after 12 weeks of rebound therapy exercise (three sessions per week) in the walking laboratory, using a seven-camera 3D motion capturing system (Qualisys motion analysis). The final data were analyzed using repeated measures ANOVA in SPSS software (significance level p < .05). Results: Rebound therapy training significantly improved all dependent variables (p < .05) except hip rotation, indicating its effectiveness for enhancing walking ability. Conclusion: Given the importance of walking function, we recommend the use of rebound therapy training as an exercise rehabilitation method for spinal cord injury patients.

Predicting Complete versus Incomplete Long-Term Functional Independence after Acute AIS Grade D Spinal Cord Injury: A Prospective Cohort Study.

Background: The proportion of patients with American Spinal Injury Association Impairment Scale (AIS) grade D traumatic spinal cord injuries (tSCI) is increasing. Although initial motor deficits can be relatively mild, some individuals fail to recover functional independence. Objectives: This study aims to identify factors associated with failure to reach complete functional independence after AIS grade D tSCI. Methods: An observational prospective cohort study was conducted at a level 1 trauma center specialized in SCI care. A prospective cohort of 121 individuals with an AIS-D tSCI was considered. The baseline characteristics, length of acute stay, need for inpatient rehabilitation, and 12-month functional status were assessed. Univariate and classification and regression tree (CART) analyses were performed to identify factors associated with reaching complete versus incomplete functional independence (defined as perfect total SCIM III score at 12-month follow-up). Results: There were 69.3%, 83.3%, and 61.4% individuals reaching complete independence in self-care, respiration/sphincter management, and mobility, respectively. A total of 64 individuals (52%) reached complete functional independence in all three domains. In the CART analysis, we found that patients are more likely to achieve complete functional independence when they have a baseline motor score ≥83 (65% individuals) and if they present fewer medical comorbidities (70% individuals if Charlson Comorbidity Index [CCI] ≤4). Conclusion: About half of individuals with AIS grade D tSCI can expect complete long-term functional independence. It is important to recognize early during acute care individuals with baseline motor score <83 or a high burden of comorbidities (CCI ≥5) to optimize their rehabilitation plan.

Automated Hand Prehension Assessment From Egocentric Video After Spinal Cord Injury.

Hand function assessments in a clinical setting are critical for upper limb rehabilitation after spinal cord injury (SCI) but may not accurately reflect performance in an individual's home environment. When paired with computer vision models, egocentric videos from wearable cameras provide an opportunity for remote hand function assessment during real activities of daily living (ADLs). This study demonstrates the use of computer vision models to predict clinical hand function assessment scores from egocentric video. SlowFast, MViT, and MaskFeat models were trained and validated on a custom SCI dataset, which contained a variety of ADLs carried out in a simulated home environment. The dataset was annotated with clinical hand function assessment scores using an adapted scale applicable to a wide range of object interactions. An accuracy of 0.551±0.139, mean absolute error (MAE) of 0.517±0.184, and F1 score of 0.547±0.151 was achieved on the 5-class classification task. An accuracy of 0.724±0.135, MAE of 0.290±0.140, and F1 score of 0.733±0.144 was achieved on a consolidated 3-class classification task. This novel approach, for the first time, demonstrates the prediction of hand function assessment scores from egocentric video after SCI.

Fisetin Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglia/Macrophage M1 Polarization and JAK2/STAT3 Signaling Pathway.

Spinal cord injury (SCI) is one of the most serious health problems, with no effective therapy. Recent studies indicate that Fisetin, a natural polyphenolic flavonoid, exhibits multiple functions, such as life-prolonging, antioxidant, antitumor, and neuroprotection. However, the restorative effects of Fisetin on SCI and the underlying mechanism are still unclear. In the present study, we found that Fisetin reduced LPS-induced apoptosis and oxidative damage in PC12 cells and reversed LPS-induced M1 polarization in BV2 cells. Additionally, Fisetin safely and effectively promoted the motor function recovery of SCI mice by attenuating neurological damage and promoting neurogenesis at the lesion. Moreover, Fisetin administration inhibited glial scar formation, modulated microglia/macrophage polarization, and reduced neuroinflammation. Network pharmacology, RNA-seq, and molecular biology revealed that Fisetin inhibited the activation of the JAK2/STAT3 signaling pathway. Notably, Colivelin TFA, an activator of JAK2/STAT3 signaling, attenuated Fis-mediated neuroinflammation inhibition and therapeutic effects on SCI mice. Collectively, Fisetin promotes functional recovery after SCI by inhibiting microglia/macrophage M1 polarization and the JAK2/STAT3 signaling pathway. Thus, Fisetin may be a promising therapeutic drug for the treatment of SCI.

Data-driven prediction of spinal cord injury recovery: An exploration of current status and future perspectives.

Spinal Cord Injury (SCI) presents a significant challenge in rehabilitation medicine, with recovery outcomes varying widely among individuals. Machine learning (ML) is a promising approach to enhance the prediction of recovery trajectories, but its integration into clinical practice requires a thorough understanding of its efficacy and applicability. We systematically reviewed the current literature on data-driven models of SCI recovery prediction. The included studies were evaluated based on a range of criteria assessing the approach, implementation, input data preferences, and the clinical outcomes aimed to forecast. We observe a tendency to utilize routinely acquired data, such as International Standards for Neurological Classification of SCI (ISNCSCI), imaging, and demographics, for the prediction of functional outcomes derived from the Spinal Cord Independence Measure (SCIM) III and Functional Independence Measure (FIM) scores with a focus on motor ability. Although there has been an increasing interest in data-driven studies over time, traditional machine learning architectures, such as linear regression and tree-based approaches, remained the overwhelmingly popular choices for implementation. This implies ample opportunities for exploring architectures addressing the challenges of predicting SCI recovery, including techniques for learning from limited longitudinal data, improving generalizability, and enhancing reproducibility. We conclude with a perspective, highlighting possible future directions for data-driven SCI recovery prediction and drawing parallels to other application fields in terms of diverse data types (imaging, tabular, sequential, multimodal), data challenges (limited, missing, longitudinal data), and algorithmic needs (causal inference, robustness).

A robust paradigm for studying regeneration after traumatic spinal cord injury in zebrafish.

BACKGROUND: Zebrafish are vertebrates with a high potential of regeneration after injury in the central nervous system. Therefore, they have emerged as a useful model system for studying traumatic spinal cord injuries. NEW METHOD: Using larval zebrafish, we have developed a robust paradigm to model the effects of anterior spinal cord injury, which correspond to the debilitating injuries of the cervical and thoracic regions in humans. Our new paradigm consists of a more anterior injury location compared to previous studies, a modified behavioral assessment using the visual motor response, and a new data analysis code. RESULTS: Our approach enables a spinal cord injury closer to the hindbrain with more functional impact compared to previous studies using a more posterior injury location. Results reported in this work reveal recovery over seven days following spinal cord injury. COMPARING WITH EXISTING METHODS: The present work describes a modified paradigm for the in vivo study of spinal cord regeneration after injury using larval zebrafish, including an anterior injury location, a robust behavioral assessment, and a new data analysis software. CONCLUSIONS: Our findings lay the foundation for applying this paradigm to study the effects of drugs, nutrition, and other treatments to improve the regeneration process.

Stage-dependent role of interhemispheric pathway for motor recovery in primates.

Whether and how the non-lesional sensorimotor cortex is activated and contributes to post-injury motor recovery is controversial. Here, we investigated the role of interhemispheric pathway from the contralesional to ipsilesional premotor cortex in activating the ipsilesional sensorimotor cortex and promoting recovery after lesioning the lateral corticospinal tract at the cervical cord, by unidirectional chemogenetic blockade in macaques. The blockade impaired dexterous hand movements during the early recovery stage. Electrocorticographical recording showed that the low frequency band activity of the ipsilesional premotor cortex around movement onset was decreased by the blockade during the early recovery stage, while it was increased by blockade during the intact state and late recovery stage. These results demonstrate that action of the interhemispheric pathway changed from inhibition to facilitation, to involve the ipsilesional sensorimotor cortex in hand movements during the early recovery stage. The present study offers insights into the stage-dependent role of the interhemispheric pathway and a therapeutic target in the early recovery stage after lesioning of the corticospinal tract.

Prediction of segmental motor outcomes in traumatic spinal cord injury: Advances beyond sum scores.

BACKGROUND AND OBJECTIVES: Neurological and functional recovery after traumatic spinal cord injury (SCI) is highly challenged by the level of the lesion and the high heterogeneity in severity (different degrees of in/complete SCI) and spinal cord syndromes (hemi-, ant-, central-, and posterior cord). So far outcome predictions in clinical trials are limited in targeting sum motor scores of the upper (UEMS) and lower limb (LEMS) while neglecting that the distribution of motor function is essential for functional outcomes. The development of data-driven prediction models of detailed segmental motor recovery for all spinal segments from the level of lesion towards the lowest motor segments will improve the design of rehabilitation programs and the sensitivity of clinical trials. METHODS: This study used acute-phase International Standards for Neurological Classification of SCI exams to forecast 6-month recovery of segmental motor scores as the primary evaluation endpoint. Secondary endpoints included severity grade improvement, independent walking, and self-care ability. Different similarity metrics were explored for k-nearest neighbor (kNN) matching within 1267 patients from the European Multicenter Study about Spinal Cord Injury before validation in 411 patients from the Sygen trial. The kNN performance was compared to linear and logistic regression models. RESULTS: We obtained a population-wide root-mean-squared error (RMSE) in motor score sequence of 0.76(0.14, 2.77) and competitive functional score predictions (AUCwalker = 0.92, AUCself-carer = 0.83) for the kNN algorithm, improving beyond the linear regression task (RMSElinear = 0.98(0.22, 2.57)). The validation cohort showed comparable results (RMSE = 0.75(0.13, 2.57), AUCwalker = 0.92). We deploy the final historic control model as a web tool for easy user interaction (https://hicsci.ethz.ch/). DISCUSSION: Our approach is the first to provide predictions across all motor segments independent of the level and severity of SCI. We provide a machine learning concept that is highly interpretable, i.e. the prediction formation process is transparent, that has been validated across European and American data sets, and provides reliable and validated algorithms to incorporate external control data to increase sensitivity and feasibility of multinational clinical trials.

How Can We Treat If We Do Not Measure: A Systematic Review of Neurogenic Bowel Objective Measures.

Background: Guidelines fail to recommend objective measures to assist with treatment of neurogenic bowel dysfunction (NBD) in spinal cord injury (SCI). Objectives: The main objective was to review the literature to identify the objective measures used in all NBD populations and to present their results and any correlations performed to validated subjective measures. Methods: A systematic review of the literature was performed in accordance with PRISMA (2020) guidelines, including all records from January 2012 to May 2023 with MeSH terms like "neurogenic bowel" indexed in the following databases: PubMed, EMBASE, CINAHL, Cochrane Central Trials Register, and ClinicalTrials.gov. Abstracts were excluded if they did not include objective measures or if they only mentioned the esophagus, stomach, and/or small bowel. Records were screened independently by at least two collaborators, and differences were resolved by unanimous agreement. Results: There were 1290 records identified pertaining to NBD. After duplicates were removed, the remaining records were screened for a total of 49 records. Forty-one records (82%) included subjective measures. Two-thirds of the articles involved the population with SCI/disease (n = 552) and one-third were non-SCI NBD (n = 476). Objective measures were categorized as (1) transit time, (2) anorectal physiology testing, and (3) miscellaneous. Of the 38 articles presenting results, only 16 (42%) performed correlations of objective measures to subjective measures. Conclusion: There is an abundance of literature supporting the use of objective outcome measures for NBD in SCI. Strong correlations of subjective measures to objective outcome measures were generally lacking, supporting the need to use both measures to help with NBD management.

Transplantation of Predegenerated Peripheral Nerves after Complete Spinal Cord Transection in Rats: Effect of Neural Precursor Cells and Pharmacological Treatment with the Sulfoglycolipid Tol-51.

Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.

Distinct brain network patterns in complete and incomplete spinal cord injury patients based on graph theory analysis.

AIMS: To compare the changes in brain network topological properties and structure-function coupling in patients with complete spinal cord injury (CSCI) and incomplete spinal cord injury (ICSCI), to unveil the potential neurobiological mechanisms underlying the different effects of CSCI and ICSCI on brain networks and identify objective neurobiological markers to differentiate between CSCI and ICSCI patients. METHODS: Thirty-five SCI patients (20 CSCI and 15 ICSCI) and 32 healthy controls (HCs) were included in the study. Here, networks were constructed using resting-state functional magnetic resonance imaging to analyze functional connectivity (FC) and diffusion tensor imaging for structural connectivity (SC). Then, graph theory analysis was used to examine SC and FC networks, as well as to estimate SC-FC coupling values. RESULTS: Compared with HCs, CSCI patients showed increased path length (Lp), decreased global efficiency (Eg), and local efficiency (Eloc) in SC. For FC, ICSCI patients exhibited increased small-worldness, clustering coefficient (Cp), normalized clustering coefficient, and Eloc. Also, ICSCI patients showed increased Cp and Eloc than CSCI patients. Additionally, ICSCI patients had reduced SC-FC coupling values compared to HCs. Moreover, in CSCI patients, the SC network's Lp and Eg values were significantly correlated with motor scores, while in ICSCI patients, the FC network's Cp, Eloc, and SC-FC coupling values were related to sensory/motor scores. CONCLUSIONS: These results suggest that CSCI patients are characterized by decreased efficiency in the SC network, while ICSCI patients are distinguished by increased local connections and SC-FC decoupling. Moreover, the differences in network metrics between CSCI and ICSCI patients could serve as objective biological markers, providing a basis for diagnosis and treatment strategies.

Astrocyte-Neuron Interactions in Spinal Cord Injury.

Spinal cord injuries cause irreversible loss of sensory and motor functions. In mammals, intrinsic and extrinsic inhibitions of neuronal regeneration obstruct neural repair after spinal cord injury. Although astrocytes have been involved in a growing list of vital homeostatic functions in the nervous system, their roles after injury have fascinated and puzzled scientists for decades. Astrocytes undergo long-lasting morphological and functional changes after injury, referred to as reactive astrogliosis. Although reactive astrogliosis is required to contain spinal cord lesions and restore the blood-spinal cord barrier, reactive astrocytes have detrimental effects that inhibit neuronal repair and remyelination. Intriguingly, elevated regenerative capacity is preserved in some non-mammalian vertebrates, where astrocyte-like glial cells display exclusively pro-regenerative effects after injury. A detailed molecular and phenotypic catalog of the continuum of astrocyte reactivity states is an essential first step toward the development of glial cell manipulations for spinal cord repair.