Methylprednisolone (MPS) has demonstrated considerable merits in the clinical treatment of spinal cord injury (SCI), yet its application is conspicuously constrained by the narrow therapeutic time window and grave side effects, such as gastrointestinal bleeding. Furthermore, the impediment posed by the blood-spinal cord barrier (BSCB) hinders the effective delivery of drugs to the injured tissue. In this study, we developed a nanodrug that exhibited programmed responsiveness to matrix metalloproteinases (MMPs) and reactive oxygen species (ROS). The surface peptide of the neutrally charged nanodrug was precisely tailored to be cleaved by MMPs at the SCI site, converting it to a robustly cationic entity, which facilitated efficient penetration of the BSCB. Subsequently, the encapsulated drugs underwent a swift release process within the SCI microenvironment, characterized by heightened ROS expression. The results showed that an impressive 7.42% of intravenously administered nanodrugs were successfully targeted to the lesion site, which inhibited cell apoptosis and fostered the survival of damaged neurons while concurrently mitigating the side effects compared to unmodified drugs. Besides, our investigation uncovered that MPS possessed the capability to modulate the polarization of macrophages, regulating the production of proinflammatory and anti-inflammatory cytokines, ultimately culminating in the restoration of motor function in injured mice. In essence, this ingeniously crafted nanodrug offers invaluable insights and guidance for the clinical management of SCI.

Objective To investigate the association between plasma fibroblast growth factor 21 (FGF21) and conventional metabolic parameters in people with chronic spinal cord injury (SCI). Design A cross-sectional study Setting An SCI-specialized rehabilitation facility in a university hospital Participants Fifty-six participants with chronic SCI (duration of SCI ≥ 1 year) Intervention Not applicable Main Outcome Measure After informed consent, demographic and SCI-related parameters were collected. Metabolic parameters, including anthropometric measures, body composition assessed by dual-energy x-ray absorptiometry, and blood tests, were evaluated. Plasma FGF21 levels were determined using an enzyme-linked immunosorbent assay (ELISA) method. Metabolic syndrome was diagnosed by the American Heart Association (AHA)/the National Cholesterol Education Program (NCEP) III Criteria. Associations between plasma FGF21 levels and other parameters were determined using multivariable linear regression analyses. Results Among 56 participants, 37 people (66%) were male. The mean (SD) age was 43.8 (10.6) years. Twelve people (21%) had tetraplegia and 14 people (15%) had complete SCI. Twelve (21%) participants were diagnosed with obesity, prediabetes, and metabolic syndrome (MetS). Using multivariable analysis adjusting for all demographic data, medical conditions, and metabolic parameters, being diagnosed with MetS had an independent positive association with plasma FGF21 level (P = 0.020, Beta coefficient = 0.776 [95%CI: 0.126–1.426]; multivariable linear regression analysis) Conclusions In people with chronic SCI, MetS is an independent positive associated factor of plasma FGF21 level, which may suggest the presence of FGF21-resistant condition. This result addresses the interesting role of FGF21 in the development of cardiometabolic diseases in people with chronic SCI.

In 2007, the Office of the Assistant Secretary of Defense issued guidance to routinely monitor post concussive symptoms following mild traumatic brain injury (mTBI). Subsequent clinical practice guidelines published as early as 2009 further underscored the importance of routine symptom monitoring following mTBI using standardized assessments such as the Neurobehavioral Symptom Inventory (NSI), though the NSI was not specifically recommended until 2015. The study objective was to describe the frequency of NSI administration, as documented in the Military Health System (MHS) electronic medical record (EMR), within one year after mTBI diagnosis among post-9/11 Active-Duty Service Members. Data for this effort were extracted from the Military Health System (MHS) Data Repository and used to identify Service Members whose first mTBI (i.e., index) was documented between Fiscal Years 2002 and 2021 (index TBI; n = 150,976). Members were excluded from the cohort for a history of a more severe TBI (n = 128,253) and/or a catastrophic injury (e.g., spinal cord injury; n = 3,805). Members were matched with data from completion of the NSI that was contained within the DoD TBI portal. The cohort was further evaluated to determine the frequency of documented NSI administration within one year of the index mTBI date. Among those with an index mTBI meeting inclusion criteria, 3,351 (2.2%) Service Members had an NSI documented within the EMR. When filtered to NSI surveys completed within 1 year of the index mTBI date, 1,182 (0.78%) NSIs were recorded. The prevalence of a matched NSI increased as time went on, with the highest number administered in 2019. Findings suggest relatively infrequent administration and documentation of the NSI following mTBI. System- and individual-level barriers may have played a role in this. Increased understanding regarding barriers and facilitators to administering and documenting the NSI within the EMR are needed to inform future implementation efforts to further measurement-based care among Service Members.

ABSTRACT Spinal cord injury (SCI) is a major global health issue with severe complications, yet effective biomarkers remain elusive. We analyzed the GSE226238 dataset from the GEO database and identified 4,621 differentially expressed genes (DEGs) between SCI and controls, comprising 2,684 upregulated and 1,577 downregulated genes. Functional enrichment analyses revealed these DEGs are predominantly involved in protein degradation pathways, immune-related processes, and ubiquitin-mediated proteolysis. Immune infiltration analysis using multiple algorithms showed significant alterations in B cells, T cells, NK cells, and neutrophils, indicating a complex immune microenvironment post-SCI. Using WGCNA, we constructed a scale-free co-expression network and identified nine modules; the green module showed the strongest positive correlation with SCI. Intersecting DEGs, WGCNA module genes, and random forest-selected features identified five candidate genes: MAP3K6, ATP5MPL, NDUFB1, RNASE2, and MIR373. Single-cell RNA sequencing further revealed that MAP3K6 exhibited the highest expression among candidates, predominantly in neuroepithelial and neuronal cells. Validation in independent GSE151371 dataset confirmed significantly elevated MAP3K6 expression in SCI, with ROC analysis demonstrating robust diagnostic efficacy (AUC = 0.918). In vitro, MAP3K6 knockdown in mouse spinal cord neuronal cells promoted cell growth and inhibited apoptosis, decreasing pro-apoptotic proteins (BAX, caspase-3, cleaved caspase-3) and increasing anti-apoptotic Bcl-2. Collectively, our multi-omics analysis integrated with experimental validation identifies MAP3K6 as a key regulator in SCI pathogenesis, offering new insights into molecular mechanisms and highlighting its potential as a diagnostic biomarker and therapeutic target.

Single-site retrospective cohort study based on medical records review from 2016-2020. Specialised rehabilitative care is required to integrate traumatic spinal cord injury (TSCI) survivors into the community. The World Health Organisation's (WHO) Rehabilitation 2030 initiative calls to strengthen rehabilitation services, and therefore, information regarding the injury profiles and length of rehabilitation stay (LORS) may assist in planning rehabilitation. The study aimed to examine the profile of individuals with TSCI, who were admitted to a rehabilitation centre, and to describe the factors associated with the LORS. Western Cape Rehabilitation centre, South Africa. The International Spinal Cord Injury Core Data Setversion 2.0 was used to extract data. One-way ANOVA and t-tests compared group means. A multiple linear regression analysis was done to account for possible intercorrelations between predictors. The population consisted predominantly of males (89.8%) in the 31--40-year-old category. Assault was the leading cause of injury (70.4%). The thoracic spine was most affected (52.4%), with complete injuries (AIS A, according to the International Standards for Neurological Classification of Spinal Cord Injury (INCSCI)) most common (42.8%). Cervical injuries were associated with significantly longer rehabilitation stays compared to thoracic or lumbar injuries. The high prevalence of assault-related etiology underscores the need for preventative strategies to reduce the incidence of TSCI among young males. The characteristics of this unique population and the factors associated with LORS have important implications for healthcare planning, particularly in optimising staff and bed resources, to enhance access to specialised care.

Motor imagery BCI enables more practical and user-friendly exoskeleton control than smartwatch for users with spinal cord injury: a preliminary study.

Gastrointestinal dysmotility and impaired gut peptide-satiety coupling in men with spinal cord injury.

Spinal cord reactive-antibodies identified by serological antigen selection show prognostic value in traumatic spinal cord injury patients.

Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis.

Pain, Daily Activities, Mobility, and Psychosocial Health in Young People With Spinal Cord Injury: A Test of Biological Sex in a Moderated Mediation Analysis.

Mechanistic study on Lnc-Gstm5 regulation of the SUV39H1/H3K9me3 axis in hyperbaric oxygen-mediated suppression of inflammatory response following spinal cord injury.

Awareness level related to spinal cord injury among emergency healthcare providers in Jordan.

Vagus nerve stimulation during rehabilitative training can improve motor function years after stroke or spinal cord injury. This open-label study examined whether vagus nerve stimulation paired with participant-selected activities of daily living in a home environment can improve task performance in participants with chronic stroke or incomplete cervical spinal cord injury. Fourteen participants were recruited from our previous randomized studies involving months of vagus nerve stimulation delivered during in-clinic therapy. Seven participants with chronic stroke and seven with chronic incomplete spinal cord injury completed 36 additional sessions of vagus nerve stimulation paired with training on a set of self-selected, high-priority activities of daily living at home. Each participant trained on 5-10 tasks. Performance was measured before and after vagus nerve stimulation + ADL therapy. Vagus nerve stimulation + activity of daily living therapy reduced time to complete trained activities of daily living by 19.8 ± 5.2% for participants with stroke and 33.8 ± 4.9% for participants with spinal cord injury. The observed gains are clinically meaningful and suggest a reduction in the functional burden of injury, which has the potential to improve independence and reduce reliance on caregivers. These initial results are sufficient to justify a randomized, sham-controlled study to evaluate whether vagus nerve stimulation during task-specific training can improve task performance and independence.

Spinal cord injury (SCI) is associated with severe immunologic changes, such as SCI-induced immune deficiency syndrome, which heightens susceptibility to infections. However, the immune components underlying this immune reorganization remain poorly defined. This study aimed to characterize immune remodeling in patients with SCI across different time points postinjury. High-dimensional flow cytometric profiling was performed on peripheral blood samples from patients with SCI in a cross-sectional observational study to assess immune changes at different postinjury time points. Patients in the subacute phase (22-67 days of postinjury [dpi]) and chronic phase (≥365 dpi) were compared with healthy, sex-matched, and age-matched controls. Alterations in the T-cell and natural killer (NK) cell compartments were observed, particularly in the subacute phase postinjury. Memory T cells and NK cells showed elevated expression of the NAD+ metabolizing enzyme CD38 and immune checkpoint molecules, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), indicating immune activation and possible exhaustion. Coexpression of CD38 and CTLA-4 on T cells was rare, suggesting distinct activation and inhibitory states. In chronic patients, we observed decreased frequencies of NK cells with no substantial changes in T cells and B cells. Notably, changes in CD38, CTLA-4, and PD-1 were no longer found in patients in the chronic phase. These findings reveal noteworthy changes in immune cell activation and exhaustion markers that may contribute to immune vulnerability after SCI, offering novel insights into potential therapeutic targets, such as NAD+ metabolism and immune checkpoint modulation.

Anti-inflammatory role of methylprednisolone in the hippocampus prevents depressive-like behavior after spinal cord injury in rats.

Panax notoginseng saponins ameliorate spinal cord injury by inhibiting JAK2/STAT3-mediated macrophage polarization: Enhanced delivery by ultrasound-targeted microbubble destruction.

Syncope is a manifestation of autonomic dysfunction after high spinal cord injury. However, it is rarely reported as a feature of postural orthostatic tachycardia syndrome (POTS) after spinal cord injury. This case report describes a male in his 50s suffering from C2 spinal cord injury who developed recurrent postural syncope post-injury. These events were characterized by orthostatic tachycardia upon standing and could even be induced by seated head-tilt maneuvers, fulfilling the diagnostic criteria for POTS. These patients have substantial risks of fall-related morbidity. Heart rate variability and sympathetic skin response assessments help elucidate the underlying autonomic pathophysiological mechanisms. Syncope may be the predominant symptom during transfers, standing, or seated head-tilt positioning. Notably, documenting heart rate fluctuations during transient syncopal events is challenging. Infections constitute established triggers for syncope. Comprehensive management strategies may achieve complete resolution of syncopal episodes.

Trunk control has consistently been rated as a priority for recovery by individuals with spinal cord injury due to its role in facilitating interactions with the environment from a seated position. Feedback control of functional neuromuscular stimulation with the networked neuroprosthesis is a promising solution for automatically stabilizing seated posture after spinal cord injury by controlling the activation of paralyzed trunk muscles via accelerometers embedded in implanted modules. This study examined the design of a control system for implanted stimulation in an individual with cervical spinal cord injury who received an Networked Neuroprosthesis. A tilt-based threshold feedback controller modulated the stimulation that activated the paralyzed hip and trunk muscles such that the controller prevented the individual's trunk from moving beyond arbitrarily defined limits of seated leaning in the sagittal and coronal planes. Findings suggest that such a controller for the networked neuroprosthesis can enable individuals with spinal cord injury to complete returns to erect sitting from approximately 30° of forward or lateral flexion without external sensors and confirms the feasibility of deploying feedback-controlled functional neuromuscular stimulation to restore motor function using the fully implanted networked neuroprosthesis system.

Spinal cord injury typically leads to neurogenic bladder dysfunction, often including detrusor-sphincter dyssynergia. Sacral anterior root stimulation can empty the neurogenic bladder, but this emptying can be impeded by reflex contractions of the urethral sphincter. The sacral sensory roots are typically transected (rhizotomy) to reduce these reflex contractions, but this rhizotomy also impairs desirable reflexes (e.g., sexual function) and sacral sensation, if present. Preclinical experiments have shown that sacral nerve stimulation at 600 Hz can promote bladder emptying while reducing urethral sphincter activity. In this proof-of-concept study, we tested 600-Hz sacral nerve stimulation to limit urethral sphincter activity in individuals with spinal cord injury who were already implanted with a sacral anterior root stimulation device. Bladder pressure, urethral pressure, rectal pressure, anal pressure, and pelvic floor electromyogram were measured in response to stimulation at 20 or 600 Hz. Stimulation was feasible and well-tolerated, and frequency appeared to have an effect on lower urinary tract and bowel function. In one participant, stimulation at 600 Hz produced a significant decrease in urethral pressure compared to 20-Hz stimulation. Further work is needed to explore the potential for this approach to improve bladder emptying efficiency for individuals with spinal cord injury and detrusor-sphincter dyssynergia.

A proactive cholinergic-like acidic fibroblast growth factor delivery system for efficient protein enrichment and native drug release in the central nervous system to promote repair of injured spinal cord.