Spinal Cord Injury Group Research Articles

Comparação da atividade muscular em bicicleta ergométrica e aparelho elíptico em indivíduos com lesão medular incompleta

Abstract Introduction Spinal cord injury generates muscle weakness, impairing orthostatism and gait. The elliptical trainer (ET) and the ergometric bicycle (EB) are rehabilitation options for this subject. Understanding the pattern of muscle activation generated by these methods is important to answer questions arising from clinical practice. Objective To verify muscle activation with ET and EB with and without electromyographic biofeedback in subjects with incomplete spinal cord injury (ISCI). Methods Cross-sectional crossover study, enrolled in Clinical Trials (NCT05118971). Subjects with spinal cord injury (incomplete spinal cord injury group - ISCIG) and without spinal cord injury (reference group - RG) were randomized into four groups: elliptical group (EG), elliptical + biofeedback group (EBG), bicycle group (BG) and bicycle + biofeedback group (BBG). Subjects were assessed for functionality by the Functional Independence Measure, injury classification by the ASIA Scale, muscle tone by the modified Ashworth scale, and muscle activity by electromyography. Results There was greater activation of the tibialis anterior on cycling compared to other modalities in ISCIG. Biofeedback offered no difference in any of the groups. In RG the vastus medialis was the most activated muscle in all modalities, with more expressive activation in the ET. In this same group, the tibialis anterior was more activated on the EB. Conclusion This study showed that both ET and EB are safe and effective in recruiting the muscles investigated, encouraging its use by rehabilitation professionals when the objective is to strength muscles involved in gait.

Expression Profiles of Long Noncoding RNAs and Messenger RNAs in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Pain Alleviating Effect of Adipose-Derived Stem Cells Transplantation on the Injured Spinal Cord: A Behavioral and Electrophysiological Evaluation.

Few studies are conducted on the efficacy of human adipose-derived stem cells (ADSCs) in spinal cord injury (SCI) management and electrophysiological changes in the spinal cord. Therefore, the present study aimed to determine the effect of ADSCs on neuropathic pain, motor function recovery, and electrophysiology assessment. For the purpose of this study, adult male Wistar rats (weight: 140-160 gr, n = 42) were randomly allocated into five groups namely intact animals, sham-operated, SCI non-treated animals, vehicle-treated (culture media), and ADSCs treated groups. One week after clips compression SCI induction, about 1×106 cells were transplanted into the spinal cord. As well, both neuropathic pain (allodynia and hyperalgesia) and motor function were measured weekly. Cavity size, ADSCs survival, and electrophysiology assessments were measured at the end of the eighth week. The transplantation of ADSCs resulted in a significant improvement in the locomotion of SCI animals (p<0.0001), mechanical allodynia (p<0.0001), cold allodynia (p<0.0001), mechanical hyperalgesia (p<0.0001), and thermal hyperalgesia (p<0.0001). The cavity size was significantly smaller among the ADSCs-treated animals (p <0.0001). The single-unit recording showed that the transplantation of ADSCs decreased wide dynamic range (WDR) in neurons and it evoked potential in response to receiving signals from Aβ (p<0.0001) and Aδ (p=0.003) C-fiber (p<0.0001) neurons. Post-discharge recorded from WDR neurons decreased after the transplantation of ADSCs (p<0.0001) and wind up in the ADSCs-treated group was lower than that of the SCI group (p=0.003). Our results showed that the transplantation of ADSCs could significantly alleviate neuropathic pain, enhance motor function recovery, and improve electrophysiology findings after SCI.

Molecular Characterization and Clinical Characteristics of m5C-Based RNA Methylation in Spinal Cord Injury: Validated by qPCR.

Aberrant patterns of 5-methylcytosine (m5C)-based ribonucleic acid (RNA) methylation have critical roles in various human diseases, but their importance in spinal cord injury (SCI) is largely unknown. We explore the expression patterns and potential roles of m5C-based regulators of RNA modification after SCI. We analyzed 16 m5C-based regulators of RNA modification in tissues with SCI and normal rats from the Gene Expression Omnibus database. We constructed a "gene signature" of m5C-based regulators of RNA modification to predict the prognosis of SCI using least absolute shrinkage and selection operator regression and random-forest strategy. We found that the m5C-related genes, deoxyribonucleic acid (DNA) methyltransferase1 (Dnmt1), methyl-CpG binding domain protein 2 (Mbd2), ubiquitin-like with PHD and ring finger domains 1 (Uhrf1), uracil-N-glycosylase (Ung), and zinc finger and BTB(brica-brac, tramtrack, and broad) domain containing 38 (Zbtb38) had high expression, and zinc finger and BTB domain containing 4 (Zbtb4) had low expression in SCI. Analysis of the correlation between the gene sets of m5C-based regulators of RNA modification and immune-cell infiltration and immune response revealed Dnmt1, DNA methyltransferases 3A (Dnmt3a), Mbd2, and Ung to be positive regulators of the immune microenvironment, and Zbtb4 may negatively regulate the immune environment. Then, two molecular subtypes were identified based on 16 m5C-regulated genes. Functional-enrichment analysis of differentially expressed genes between different patterns of m5C-based modification was undertaken. Through the creation of a protein-protein interaction network, we screened 11 hub genes. We demonstrated their importance between SCI group and sham group using real-time reverse transcription-quantitative polymerase chain reaction in rat model. Expression of hub genes did not correlate with mitophagy but was positively correlated with endoplasmic reticulum stress (ERS), which suggested that there may be differences in ERS between different patterns of m5C-based modification. This present study explored and discovered the close link between m5C regulators-related genes and SCI. We also hope our findings may contribute to further mechanistic and therapeutic research on the role of key m5C regulators after SCI.

Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion.

Spinal cord injury (SCI) produces diminished bone perfusion and bone loss in the paralyzed limbs. Activity-based physical therapy (ABPT) modalities that mobilize and/or reload the paralyzed limbs (e.g., bodyweight-supported treadmill training (BWSTT) and passive-isokinetic bicycle training) transiently promote lower-extremity blood flow (BF). However, it remains unknown whether ABPT alter resting-state bone BF or improve skeletal integrity after SCI. Four-month-old male Sprague-Dawley rats received T 9 laminectomy alone (SHAM; n = 13) or T 9 laminectomy with severe contusion SCI ( n = 48). On postsurgery day 7, SCI rats were stratified to undergo 3 wk of no ABPT, quadrupedal (q)BWSTT, or passive-isokinetic hindlimb bicycle training. Both ABPT regimens involved two 20-min bouts per day, performed 5 d·wk -1 . We assessed locomotor recovery, bone turnover with serum assays and histomorphometry, distal femur bone microstructure using in vivo microcomputed tomography, and femur and tibia resting-state bone BF after in vivo microsphere infusion. All SCI animals displayed immediate hindlimb paralysis. SCI without ABPT exhibited uncoupled bone turnover and progressive cancellous and cortical bone loss. qBWSTT did not prevent these deficits. In comparison, hindlimb bicycle training suppressed surface-level bone resorption indices without suppressing bone formation indices and produced robust cancellous and cortical bone recovery at the distal femur. No bone BF deficits existed 4 wk after SCI, and neither qBWSTT nor bicycle altered resting-state bone perfusion or locomotor recovery. However, proximal tibia BF correlated with several histomorphometry-derived bone formation and resorption indices at this skeletal site across SCI groups. These data indicate that passive-isokinetic bicycle training reversed cancellous and cortical bone loss after severe SCI through antiresorptive and/or bone anabolic actions, independent of locomotor recovery or changes in resting-state bone perfusion.

A Nationwide Register-Based Study Of The Socio-Economic Consequences Of Traumatic And Non-Traumatic Spinal Cord Injury

<h3>Research Objectives</h3> To investigate the socioeconomic consequences of traumatic (tSCI) and non-traumatic (ntSCI) spinal cord injury (SCI) in relation to health care costs, risk of job loss, and divorce. <h3>Design</h3> A nationwide population-based register study. <h3>Setting</h3> General community, Denmark. <h3>Participants</h3> All survivors of SCI (tSCI: n=838; ntSCI: n=913) admitted for specialized SCI rehabilitation during the years 2008-2018 were included. Furthermore, a cohort of relatives to survivors of SCI (n=3,084) was identified using national registers. Using propensity score matching (including age, gender, marital status, region, labor market affiliation, and months of education) control groups for SCI survivors (n=8,139) and their relatives (n=15,921) were identified. Data were retrieved up to two years before the injury year and up to four years after the injury year. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Utilization of health care costs (including hospital services, use of general practitioner and practicing specialists, and prescribed medication), risk of job loss, and risk of divorce. <h3>Results</h3> Survivors of tSCI and ntSCI had significantly increased health care costs up to two years before the injury and the following four years after injury (all p-values < 0.0001). Survivors of SCI had nine times higher risk of losing their job compared to their controls during the three years after the injury year (OR=9.26; 95% CI: 7.70 to 11.15), and risk of divorce was also higher (OR=1.58; 95% CI: 1.09 to 2.29) the three following years, but only significant for the ntSCI group. No significant differences on health care cost and job loss between the group of relatives of SCI survivors and their controls were found. <h3>Conclusions</h3> In conclusion, the SCI group had significantly higher utilization of health care costs, both pre-morbidly and post-injury. The SCI group also had an increased risk of job loss, which emphasizes how the socioeconomic consequences of SCI are pervasive and long-lasting. <h3>Author(s) Disclosures</h3> No conflicts of interest for all authors

Health-related Self-efficacy following Stroke, Traumatic Brain Injury, and Spinal Cord Injury

<h3>Research Objectives</h3> To examine baseline self-efficacy for individuals with different neurological diagnoses prior to enrollment in a healthy lifestyle intervention and associations with demographics, injury characteristics, and physiologic variables. <h3>Design</h3> Cross-sectional analysis of baseline data prior to enrollment in three adapted healthy lifestyle interventions. <h3>Setting</h3> Community dwelling adults in the Dallas-Fort Worth metropolitan area. <h3>Participants</h3> Participants with history of stroke (CVA), traumatic brain injury (TBI), or spinal cord injury (SCI) were enrolled into three healthy lifestyle intervention studies, resulting in a total of 221 participants across three studies: n=65 (29%) in the CVA group, n=57 (26%) in the TBI group, n=99 (45%) in the SCI group. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Health-related total self-efficacy as measured by the Self Rated Abilities for Health Practices Scale and physiologic measures. <h3>Results</h3> Among the three groups, there were statistically significant differences in age, number of household members, time since injury, sex, race, marital status, and employment status. Blood pressure was lowest for individuals with SCI and HbA1C was highest for those with CVA. A linear regression model showed an association between injury type and total self-efficacy score after controlling for covariates. On average, individuals with SCI had an 11.2 point lower health-related total self-efficacy score (CI: -17.4, -5.0, p < 0.001) and those with TBI has a 9.5 point lower score (CI: -16.7, -2.4, p = .009) as compared to those with CVA. <h3>Conclusions</h3> Type of injury was significantly related to health-related self-efficacy, suggesting that following acquired brain injury or spinal cord injury one's perception of eating a healthy diet, exercising, or maintaining health may differ based on different functional outcomes or experiences. <h3>Author(s) Disclosures</h3> This work was supported by three grants from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant numbers 90DPTB0013, 90IFRE0021, 90IFRE0022). The contents of this presentation do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government.

Longitudinal Median Nerve Ultrasound Changes in Individuals With Spinal Cord Injury and an Age- and Sex-Matched Nondisabled Cohort.

To assess the natural history for development of carpal tunnel syndrome (CTS) in persons with acute spinal cord injury (SCI) at 1 year postdischarge from initial rehabilitation and to assess baseline median nerve (MN) cross-sectional area (CSA) above/below 10 mm2 correlates with any longitudinal changes in quantitative ultrasound (US) of the MN. A prospective cohort study of persons with acute SCI evaluated for CTS using quantitative US and compared to a group without SCI (non-SCI). Academic medical center. N=69 total (N=34 SCI, N=35 non-SCI). The average age in both groups was 28 and the SCI group included 30 males and 2 females and the non-SCI group included 30 males and 3 females. Not applicable. The primary outcome was the change in quantitative US parameters of the MN, including CSA and grayscale, from baseline to 1-year follow-up in those with SCI and those without SCI. CTS symptomatology and physical exam sum score and US measures for dominant and nondominant arms were considered secondary outcomes. The SCI had darker nerves at baseline (P=.036, nondominant), greater CTS symptoms at follow-up (P≤.036, bilateral), and no differences in all change scores (all P≥.056). Individuals with smaller nerves at baseline had larger increases in nerve size (P=.029, nondominant) vs those with larger nerves. Change in CTS symptoms CSA (nondominant) and nerve echogenicity (dominant) were inversely associated with their respective baseline values (all P≤.045). We observed few differences between the SCI group and the non-SCI control group and between those with smaller vs larger MN. In general, MN pathology changes (CTS symptoms and US variables) over 1 year were more common in the nondominant arm and appear to be a function of MN pathology at enrollment. Individuals with SCI may experience increased CTS symptoms as soon as 1 year after injury.

Clinical Utility of Patient-Reported Outcome Measures Used for Tendon and Nerve Transfers for Tetraplegia in New Zealand

This study determines the clinical utility of patient-reported outcome measures used to measure outcomes of upper extremity (UE) reconstructive procedures in individuals with tetraplegia. The patient-reported outcome measures are the Canadian Occupational Performance Measure, the Capabilities of Upper Extremity Questionnaire (CUE-Q), and the Personal Wellbeing Index. Retrospective data of 43 individuals with spinal cord injury (SCI) levels C4-C7 tetraplegia, and American Spinal Injury Association Impairment Scale grades A-D who had upper limb reconstructive surgery were reviewed. Participants were grouped according to their SCI level and resultant surgical procedures into higher SCI severity and lower SCI severity groups. The mean age of participants was 26.3 years (SD 13.4; range 13-64 years). The higher-severity SCI group required elbow and hand reconstruction surgery, whereas the lower-severity group only required hand reconstruction surgery. Important differences in Canadian Occupational Performance Measure priorities were identified between the higher and lower SCI severity groups. Question redundancy was evident with the CUE-Q. The self-report Personal Wellbeing Index captures the possible impacts of improved UE function on an individual's perceived sense of personal wellbeing. In this patient-reported outcome measure analysis, we found that the level of impairment influences patient priorities. Functional measures ought to consider UE impairment and personal wellbeing as a construct in this population, given the demands of surgery. Prognostic II.

Aripiprazole Improves Spinal Cord Injury in Rats: Involvement of Inflammatory Pathways

Macrophages and glial activation contribute to the pathophysiology of spinal cord injury (SCI). Some preclinical studies have shown the anti-inflammatory effects of aripiprazole (ARP). In the current study, we evaluated the anti-inflammatory effects of ARP in a rat SCI model. Forty male Wistar rats underwent either T9 vertebra laminectomy or were used as a sham-operated group without laminectomy. There were four major groups in this study: a sham-operated, three treatments (normal saline [vehicle] control versus ARP 10 and 20 mg/kg/day for three days after surgery, first dose 30 minutes post-surgery) SCI groups. We evaluated locomotor scaling and neuropathic pain behavioral tests over 28 days. On Day 28, tissue samples were investigated for neuroinflammatory and histopathology changes through flow cytometry and ELISA. ARP (10 and 20 mg/kg/day, 3 days) treatment significantly reduced locomotors disability (P&lt;0.01) and mechanical (P&lt;0.01) and thermal allodynia (P&lt;0.001) scores. Additionally, Levels of tumor necrosis factor (TNF)-α level and interleukin (IL)-10 were significantly altered in ARP-treated spinal cord tissues 28 days after SCI (P&lt;0.01). Moreover, spinal cord tissue expression of M1 and M2 macrophages, as well as M1/M2 ratio, were reduced in ARP-treated SCI animals, concurrent with decreased M1 and increased M2 and M1/M2 in dorsal root ganglion (P&lt;0.001). Our study indicates that ARP has therapeutic effects on SCI via the reduction of neuroinflammation and SCI sensory and locomotor abnormalities.

Paired pulse transcranial magnetic stimulation in the assessment of biceps voluntary activation in individuals with tetraplegia.

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS.

Hyperbaric Oxygen Treatment in Spinal Cord Injury Recovery: Profiling Long Noncoding RNAs.

A functional, transcriptome, and long noncoding RNAs (lncRNAs) expression analysis in the spinal cord of mice after hyperbaric oxygen (HBO) treatment. We aimed to explore the mechanism by which HBO treats spinal cord injury (SCI) at the level of lncRNAs. Immense amounts of research have established that HBO treatment promotes the recovery of neurological function after SCI. The mechanism of action remains to be clarified. High-throughput RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to profile lncRNA expression and analyze biological function in the spinal cords of mice from sham-operated, SCI, and HBO-treated groups. The differential expression of lncRNA between the groups was assessed using real-time quantitative polymerase chain reaction. Differential expression across 577 lncRNAs was identified among the three groups. GO analysis showed that free ubiquitin chain polymerization, ubiquitin homeostasis, DNA replication, synthesis of RNA primer, single-stranded telomeric DNA binding, and alpha-amylase activity were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis displayed that vitamin B6 metabolism, one carbon pool by folate, DNA replication, lysine degradation, beta-alanine metabolism, fanconi anemia pathway, and Notch signal pathway were the main pathways with enrichment significance. LncRNAs NONMMUT 092674.1, NONMMUT042986.2, and NONMMUT018850.2 showed significantly different expression between the SCI and the other two groups (P<0.05, <0.01). This study is the first to determine the expression profiles of lncRNAs in the injured spinal cord after HBO treatment. We identified several important dysregulated lncRNAs in this setting. These results help us better understand the mechanism by which HBO treats SCI and provide new potential therapeutic targets for SCI.

Expression of transforming growth factor-β1 and autophagy markers in the bladder of rats with neurogenic lower urinary tract injury.

This study was conducted to explore the expression of transforming growth factor-beta 1 (TGF-β1) and its correlation with autophagy markers in the bladder of rats with neurogenic lower urinary tract dysfunction (NLUTD) post spinal cord injury (SCI). A total of 36 male Wistar rats were randomly divided into the SCI group and control group. Rats in the SCI group were subjected to T10-T11 spinal cord transection. At day 1, 4, and 7, 6 rats were euthanized daily and the Basso, Beattie and Bresnahan score (BBB score), post-void residual (PVR), urinary bladder function score (UBFS) and bladder weight were assessed. The expression TGF-β1 and autophagy markers were evaluated by immunofluorescence staining, Western bolt, and qRT-PCR. A total of 36 male Wistar rats were randomly divided into the SCI group and control group, with three time points in each group. Not applicable. SCI modeling impaired the motor function of the hind limbs and the bladder function of rats. NLUTD muscle exhibited a punctated immunostaining pattern for LC3, suggesting the accumulation of autophagosomes. Our results further indicated that compared with the control group, the expression levels of TGF-β1 and LC3 were increased, while the level of P62 was decreased after SCI modeling. TGF-β1 was significantly increased in SCI rats with NLUTD and was correlated with autophagy markers LC3 and p62.

Interaction between increasing body mass index and spinal cord injury to the probability of developing a diagnosis of nonalcoholic fatty liver disease.

The prevalence of obesity and comorbidities is high in the population with spinal cord injury (SCI). We sought to determine the effect of SCI on the functional form of the relationship between body mass index (BMI) and risk of developing nonalcoholic fatty liver disease (NAFLD), and assess whether SCI-specific mapping of BMI to risk of developing NAFLD is needed. Longitudinal cohort study comparing Veterans Health Administration patients with a diagnosis of SCI to a 1:2 matched control group without SCI. The relationship between BMI and development of NAFLD at any time was assessed with propensity score matched Cox regression models; NAFLD development at 10-year with a propensity score matched logistic model. The positive predictive value of developing NAFLD at 10years was calculated for BMI 19-45kg/m2. 14,890 individuals with SCI met study inclusion criteria, and 29,780 Non-SCI individuals in matched control group. Overall, 9.2% in SCI group and 7.3% in Non-SCI group developed NAFLD during the study period. A logistic model assessing the relationship between BMI and the probability of developing a diagnosis of NAFLD demonstrated that the probability of developing disease increased as BMI increased in both cohorts. The probability was significantly higher in the SCI cohort at each BMI threshold (p<0.01), and increased at a higher rate compared with the Non-SCI cohort as BMI increased 19-45kg/m2. Positive predictive value for developing a diagnosis of NAFLD was higher in the SCI group for any given BMI threshold from 19kg/m2 to BMI 45kg/m2. The probability of developing NAFLD is greater in individuals with SCI than without SCI, at every BMI level 19kg/m2 to 45kg/m2. Individuals with SCI may warrant a higher level of suspicion and closer screening for NAFLD. The association of SCI and BMI is not linear.

Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise, as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age- and sex-matched sham-operated controls. Skeletal parameters, locomotor function, and serum cytokine levels were assessed at both subchronic (30 days) and chronic (180 days) time points post-injury. We hypothesized that SCI would lead to a dramatic loss of bone immediately after injury in all SCI groups, with inflammaging leading to greater loss in middle-aged SCI rats. We also predicted that whereas younger rats might re-establish bone properties in more chronic phases of SCI, middle-aged rats would not. Supporting these hypothesis, trabecular bone volume was significantly lower in male and young female SCI rats early after injury. Contrary to our hypothesis, however, there was greater loss of trabecular bone volume, relative to age-matched shams, in young compared with middle-aged SCI rats, with no effects of SCI on trabecular bone volume in middle-aged female rats. Moreover, despite recovery of weight-supported locomotor activity, bone loss persisted into the chronic phase of injury for the young rats. Bone formation rates were lower in young male SCI rats, regardless of the time since injury, whereas both young and middle-aged female SCI rats had lower bone formation in the subchronic but not the chronic phase of SCI. In middle-aged rats, SCI-induced higher osteoclast surfaces, which also persisted into the chronic phase of SCI in middle-aged females. Neither age nor SCI-induced increases in inflammation seemed to be associated with bone loss. In fact, SCI had more dramatic and persistent effects on bone in male rats, whereas aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.

Characteristics of Pediatric Spinal Cord Injury in South Korea: A Single-Centered Study.

To determine the characteristics of pediatric spinal cord injury (SCI) in South Korea from 1990 to 2019. This single-centered retrospective study included pediatric SCIs. Individuals were divided into the following five groups according to onset age: ≤5, 6-12, 13-14, 15-17, and 18-19 years. The severity of complete injury was graded according to the American Spinal Injury Association impairment scale A (AIS A). Incomplete injury was graded according to AIS B, C, and D. Pearson chi-square test was used for statistical analysis. Of the 267 individuals included, 216 (80.9%) had traumatic SCIs (male-to-female ratio of 3.2:1), and 51 (19.1%) had non-traumatic SCIs (male-to-female ratio of 0.7:1). In the traumatic SCI group, 192 (88.9%) individuals were ≥15 years at the time of injury (males, 78.6%). The most common etiologies of traumatic SCIs, ranging from most to least common, were accidents related to motorcycles, falls, cars, and diving. In the non-traumatic SCI group, inflammatory (33.3%) and neoplastic (25.5%) etiologies were found to be the most common ones. We found that traumatic SCIs incidence in the pediatric population was high, particularly in male individuals aged 15-19 years. The non-traumatic SCIs mostly cause paraplegia and incomplete injury. Therefore, it can be used as a basic data for the evaluation, treatment and prevention strategy of pediatric patients with SCI.

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.

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). 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. 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. 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.

Hyperbaric Oxygen Therapy-Induced Molecular and Pathway Changes in a Rat Model of Spinal Cord Injury: A Proteomic Analysis.

Hyperbaric Oxygen Therapy (HBOT) has definitive therapeutic effects on spinal cord injury (SCI), but its mechanism of action is still unclear. Here, we've conducted a systemic proteomic analysis to identify differentially expressed proteins (DEPs) between SCI rats and HBOT + SCI rats. The function clustering analysis showed that the top enriched pathways of DEPs include oxygen transport activity, oxygen binding, and regulation of T cell proliferation. The results of functional and signal pathway analyses indicated that metabolic pathways, thermogenesis, LXR/RXR activation, acute phase response signaling, and the intrinsic prothrombin pathway in the SCI + HBOT group was higher than SCI group.

Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury.

This study is to investigate the changes of lymphocyte subsets and the gut microbiota in Chinese Han patients with spinal cord injury (SCI). We enrolled 23 patients with SCI and 21 healthy controls. Blood and fecal samples were collected. The proportion of lymphocyte subsets was detected by flow cytometry. 16S rDNA sequencing of the V4 region was used to analyze the gut microbiota. The changes of the gut microbiota were analyzed by bioinformatics. Correlation analysis between gut microbiota and lymphocyte subsets was performed. CD4 + cells, CD4 + /CD8 + ratio and CD4 + CD8 + cells in peripheral blood of SCI patients were significantly lower than those of the control group (P < 0.05). There was no significant difference in B cells and CIK cells between the SCI group and the control group. The gut microbiota community diversity index of SCI patients was significantly higher than that of healthy controls. In SCI patients, the relative abundance of Lachnospiraceae (related to lymphocyte subset regulation), Ruminococcaceae (closely related to central nervous system diseases), and Escherichia-Shigella (closely related to intestinal infections) increased significantly, while the butyrate producing bacteria (Fusobacterium) that were beneficial to the gut were dramatically decreased. Correlation analysis showed that the five bacterial genera of SCI patients, including Lachnospiraceae UCG-008, Lachnoclostridium 12, Tyzzerella 3, Eubacterium eligens group, and Rumencocciucg-002, were correlated with T lymphocyte subsets and NK cells. In the SCI group, the flora Prevotella 9, Lachnospiraceae NC2004 group, Veillonella, and Sutterella were positively correlated with B cells. However, Fusobacterium and Akkermansia were negatively correlated with B cells. Moreover, Roseburia and Ruminococcaceae UCG-003 were positively correlated with CIK cells. Our results suggest that the gut microbiota of patients with SCI is associated with lymphocyte subsets. Therefore, it is possible to improve immune dysregulation in SCI patients by modulating gut microbiota, which may serve as a new therapeutic method for SCI.

A comprehensive visual report of urodynamic study in rats with spinal cord injury

Abstract Objectives Spinal cord injury (SCI) is one of the most debilitating and expensive traumatic conditions. Chronic complications after SCI have a particularly negative impact on patients’ functional independence and quality of life. Urodynamic study (UDS) provides a quantitative assessment of lower urinary tract function in these patients. In many fields, animal models are considered a precursor to clinical trials, so research using laboratory animals play a major role in knowledge acquisition. Materials and methods Twelve female Wistar rats (13 weeks old, 220–270 g) were divided randomly into 2 groups: sham or SCI. The sham-operated group underwent a laminectomy at T9–T10 without any spinal cord damage, while the SCI group underwent a complete transection at the T9–T10 vertebral level. We performed cystometry in all animals at the end of the fourth week. In this article, we visualize all procedures for catheter implementation and UDS in animals for the first time at Tabriz University of Medical Sciences, Iran, using a locally developed animal UDS device. Results The UDS results showed that the bladders in the SCI group were overactive and that peak and baseline pressures increased significantly in rats with SCI when compared with the sham group (p &lt; 0.05 for all). Conversely, significant reductions in bladder compliance and intercontraction interval were observed in the SCI group (p &lt; 0.05 for both). Conclusions This comprehensive visual report will be very useful to all researchers in the field of urology. Furthermore, the measurable variables of the UDS device have been described in this study.