Influence of the Type of Disability and Sporting Discipline on Lipid Profile in a Cohort of Italian Paralympic Athletes.

Dyslipidemia is the most frequent cardiovascular (CV) risk factor in able-bodied athletes and is frequently undertreated, resulting in an underestimated risk of atherosclerosis-related diseases. Data on lipid profile in Paralympic athletes are lacking. Our study aimed to identify the prevalence of dyslipidemia and the influence of disability type and sporting discipline in Paralympic athletes. We evaluated 289 athletes who participated in the Paralympic Games from London 2012 to Beijing 2022. All athletes underwent clinical/physical evaluation, blood tests, and body composition analysis. They were divided into different groups based on sports disciplines and disability type (spinal cord injuries [SCIs] and non-SCIs [NSCIs]). Among the Paralympic athletes, 34.6% had a low-density lipoprotein (LDL) level ≥115 mg/100 ml. They were older (38.1 ± 9.2 vs 30.6 ± 9.6, p = 0.001) and had a higher CV risk. Athletes with SCI showed similar total cholesterol and triglycerides, higher LDL (110.9 ± 35.2 vs 102.7 ± 30.6 mg/100 ml, p = 0.03) and lower high-density lipoprotein (HDL) (53.6 ± 13.6 vs 60.5 ± 15.4 mg/100 ml, p = 0.001) than those with NSCI. Endurance athletes had lower LDL, the highest HDL, and the lowest triglycerides and LDL/HDL ratio compared with other sports disciplines. A mean follow-up of 61.5 ± 30.5 months was available in 47% athletes, and 72.7% of the athletes with dyslipidemia continued to present altered LDL values at follow-up. In conclusion, dyslipidemia is the most common CV risk factor in the Paralympics, affecting 35% of athletes, with only mild lipid changes over a medium-term time. The type of disability and sporting discipline has an impact on lipids, improving HDL and reducing LDL, with a better profile observed in NSCI and endurance athletes.

Decreased Adiponectin Levels Are a Risk Factor for Cognitive Decline in Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI) has become popular in recent years, and cognitive decline is a common complication. Adiponectin is a common protein hormone involved in the course of many diseases, but its relationship with SCI has not yet been elucidated. The purpose of our prospective study is to explore whether adiponectin can be used as a biomarker of cognitive decline in SCI. METHODS: A total of 64 healthy volunteers and 92 patients with acute SCI were recruited by us. Serum adiponectin levels, demographic data (age and gender), lifestyle (smoking and drinking), medical history (diabetes and hypertension), and clinical baseline data (low-density lipoprotein, high-density lipoprotein, and fasting blood glucose) were recorded. Three months after enrollment, we used the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function. Based on a quarter of the serum adiponectin levels, SCI patients were divided into 4 groups, and the differences in their MoCA scores were compared. In addition, we used multivariate linear regression to predict the risk factors of the MoCA score. RESULTS: The serum adiponectin level (6.1 ± 1.1 µg/ml) of SCI patients was significantly lower than that of the healthy control group (6.7 ± 0.9 µg/ml), and there was a significant difference between the two (p < 0.001). The group with higher serum adiponectin levels after 3 months of spinal cord injury had higher MoCA scores. Multivariate regression analysis showed that serum adiponectin level is a protective factor for cognitive function after SCI (ß = 0.210, p = 0.043). CONCLUSIONS: Serum adiponectin levels can be used as an independent predictor of cognitive function in patients with acute SCI.

Investigation of the blood proteome in response to spinal cord injury in rodent models.

STUDY DESIGN: Explanatory and mechanistic study. OBJECTIVES: A better understanding of the 'whole-body' response following spinal cord injury (SCI) is needed to guide future research aimed at developing novel therapeutic interventions and identifying prognostic indicators for SCI. This study aimed to characterise the blood proteome following contusion or complete SCI compared to a sham injury in rat models. SETTING: United Kingdom. METHODS: Pooled blood samples from one and seven days after a contusion (serum; n = 5) or from 14 days and 112 days post-complete transection SCI (plasma; n = 8) and their sham-injured counterparts were subjected to independent iTRAQ nanoflow liquid chromatography tandem mass-spectrometry proteomic analyses. Pathway analyses of the proteins that were differentially abundant between SCI and their matched sham injured counterparts were completed to indicate biological pathways that may be changed in response to SCI. RESULTS: Eleven and 42 proteins were differentially abundant (≥±2.0 FC; p ≤ 0.05) between the contusion SCI and sham injured animals at 24 h and seven days post-injury, respectively. Seven and tweleve proteins were differentially abundant between complete and sham injured rats at 14 and 112 days post-injury, respectively. Acute-phase response signalling and Liver X Receptor/Retinoic X Receptor activation were identified as differentially regulated pathways in both models of SCI. CONCLUSIONS: We have utilised longitudinal preclinical SCI models to provide an insight into the blood proteome changes that result following SCI and to highlight a number of biological pathways of interest for future studies.

Regulation of Inflammasomes by Application of Omega-3 Polyunsaturated Fatty Acids in a Spinal Cord Injury Model.

Omega-3 polyunsaturated fatty acids (PUFA n3) ameliorate inflammation in different diseases and potentially improve neurological function after neuronal injury. Following spinal cord injury (SCI), inflammatory events result in caspase-1 mediated activation of interleukin-1 beta (IL-1b) and 18. We aim to evaluate the neuroprotective potency of PUFA n3 in suppressing the formation and activation of inflammasomes following SCI. Male Wistar rats were divided into four groups: control, SCI, SCI+PUFA n3, and SCI+Lipofundin MCT (medium-chain triglyceride; vehicle). PUFA n3 or vehicle was intravenously administered immediately after SCI and every 24 h for the next three days. We analyzed the expression of NLRP3, NLRP1, ASC, caspase-1, IL-1b, and 18 in the spinal cord. The distribution of microglia, oligodendrocytes, and astrocytes was assessed by immunohistochemistry analysis. Behavioral testing showed significantly improved locomotor recovery in PUFA n3-treated animals and the SCI-induced upregulation of inflammasome components was reduced. Histopathological evaluation confirmed the suppression of microgliosis, increased numbers of oligodendrocytes, and the prevention of demyelination by PUFA n3. Our data support the neuroprotective role of PUFA n3 by targeting the NLRP3 inflammasome. These findings provide evidence that PUFA n3 has therapeutic effects which potentially attenuate neuronal damage in SCI and possibly also in other neuronal injuries.

Higher Physical Activity Level Improves Leptin Concentrations in Spinal Cord Injury Subjects.

The present study was designed to compare the body composition and indicators of chronic inflammatory grade, such as leptin, adiponectin, and resistin concentrations in irregularly active and active SCI subjects. Thirty-two male subjects participated in this study. They were divided into three groups: able-bodied control irregularly active (control, n = 11), irregularly active with SCI (SCI-IA, n = 8), and physically active with SCI (SCI-PA, n = 13). The enzyme-linked immunosorbent assay (ELISA) assessed serum concentrations of leptin, adiponectin, and resistin. All volunteers performed the maximum oxygen uptake (VO2max) test, 24 h total energy expenditure (TEE), and body composition by skinfold thicknesses. Leptin concentrations were higher in the SCI-IA group when compared to the other groups, while no significant differences were found between the SCI-PA and control cohorts. In addition, no significant differences were found among groups for serum adiponectin and resistin concentrations either. The SCI-PA group showed significantly higher values for TEE and VO2max when compared to the other groups. Percentages of body fat and circumference were decreased in the control and SCI-PA groups when compared to the SCI-IA cohort. Associations between leptin and cardiorespiratory capacity and anthropometric markers were also observed. Our findings highlight that the lack of physical activity in the SCI subjects leads to poor general physical fitness and higher levels of body adiposity, which may induce hyperleptinemia, an essential marker for cardiometabolic disorders.

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury.

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme-linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet.

Serum Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein Are Related to the Neurological Impairment and Spinal Edema after Traumatic Spinal Cord Injury.

Neurological examination in the acute phase after spinal cord injury (SCI) is often impossible and severely confounded by pharmacological sedation or concomitant injuries. Therefore, diagnostic biomarkers that objectively characterize severity or the presence of SCI are urgently needed to facilitate clinical decision-making. This study aimed to determine if serum markers of neural origin are related to: 1) presence and severity of SCI, and 2) magnetic resonance imaging (MRI) parameters in the very acute post-injury phase. We performed a secondary analysis of serological parameters, as well as MRI findings in patients with acute SCI (n = 38). Blood samples were collected between Days 1-4 post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament light protein (NfL) were determined. A group of 41 age- and sex-matched healthy individuals served as control group. In the group of individuals with SCI, pre-operative sagittal and axial T2-weighted and sagittal T1-weighted MRI scans were available for 21 patients. Serum markers of neural origin are different among individuals who sustained traumatic SCI depending on injury severity, and the extent of the lesion according to MRI in the acute injury phase. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) produced preliminary cut-off values for NfL (75.217 pg/mL) and GFAP (73.121 pg/mL), allowing a differentiation between individuals with SCI and healthy controls within the first 4 days after SCI. Serum proteins NfL and GFAP qualify as diagnostic biomarkers for the presence and severity of SCI in the acute post-injury phase, where the reliability of clinical exams is limited.

The Prognostic Value of Leucine-Rich α2 Glycoprotein 1 in Pediatric Spinal Cord Injury.

OBJECTIVE: Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). METHODS: This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. RESULTS: All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 µg/ml. CONCLUSIONS: Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Predicting neurological recovery after traumatic spinal cord injury by time-resolved analysis of monocyte subsets.

Monocytes and lymphocytes elicit crucial activities for the regenerative processes after various types of injury. The survival of neurons exposed to mechanical and oxidative stress after traumatic spinal cord injury depends on a multitude of factors. In this study, we sought to evaluate a correlation between remission after traumatic spinal cord injury and the dynamics of monocyte subsets in respect to the lymphocytes' responsive potential, cytokine expression, patterns of trace element concentration and clinical covariates. We examined prospectively 18 (three female, 15 male) patients after traumatic spinal cord injury. Blood samples were drawn at admission and 4 h, 9 h, 12 h, 1 and 3 days as well as 1 and 2 weeks and 1, 2 and 3 months after the trauma. Analysis of cytokines (CCL2, IL-10, enolase 2, CXCL12, TGF-ß1, TGF-ß2) was performed using a multiplex cytokine panel. Plasma trace element concentrations of selenium, copper and zinc were determined by total reflection X-ray fluorescence analysis; neopterin, selenoprotein P (SELENOP) and ceruloplasmin (CP) by enzyme-linked immunosorbent assay; and selenium binding protein 1 (SELENBP1) by luminometric immunoassay. The responsive potential of lymphocytes was assessed using transformation tests. The monocyte subsets (classical, intermediate, and non-classical) and expression of CD14, CD16, CXCR4 and intracellular IL-10 were identified using a multi-colour flow cytometry analysis. The dynamics of the cluster of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes differed significantly between patients with an absence of neurological remission (G0) from those with an improvement (G1) by 1 or 2 American Spinal Injury Association Impairment Scale (AIS) steps (Kruskal-Wallis Test, P = 0.010, G0 < G1, AIS+: 1 < G1, AIS+: 2) in the first 24 h. These dynamics were associated inversely with an increase in enolase and SELENBP1 14 days after the injury. In the elastic net regularized model, we identified an association between the increase of a subpopulation of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes and exacerbated immune response within 24 h after the injury. These findings were reflected in the consistently elevated response to mitogen stimulation of the lymphocytes of patients with significant neurological remission. Early elevated concentrations of CD14-/CD16+/IL10+/CXCR4int monocytes were related to higher odds of CNS regeneration and enhanced neurological remission. The cluster dynamics of CD14-/CD16+/IL10+/CXCR4int monocytes in the early-acute phase after the injury revealed a maximum of prognostic information regarding neurological remission (mean parameter estimate: 0.207; selection count: 818/1000 repetitions). We conclude that early dynamics in monocyte subsets allow a good prediction of recovery from traumatic spinal cord injury.

Natural Progression of Routine Laboratory Markers after Spinal Trauma: A Longitudinal, Multi-Cohort Study.

Our objective was to track and quantify the natural course of serological markers over the 1st year following spinal cord injury. For that purpose, data on serological markers, demographics, and injury characteristics were extracted from medical records of a clinical trial (Sygen) and an ongoing observational cohort study (Murnau study). The primary outcomes were concentration/levels/amount of commonly collected serological markers at multiple time points. Two-way analysis of variance (ANOVA) and mixed-effects regression techniques were used to account for the longitudinal data and adjust for potential confounders. Trajectories of serological markers contained in both data sources were compared using the slope of progression. Our results show that, at baseline (≤ 2 weeks post-injury), most serological markers were at pathological levels, but returned to normal values over the course of 6-12 months post-injury. The baseline levels and longitudinal trajectories were dependent on injury severity. More complete injuries were associated with more pathological values (e.g., hematocrit, ANOVA test; χ2 = 68.93, df = 3, adjusted p value <0.001, and χ2 = 73.80, df = 3, adjusted p value <0.001, in the Sygen and Murnau studies, respectively). Comparing the two databases revealed some differences in the serological markers, which are likely attributable to differences in study design, sample size, and standard of care. We conclude that because of trauma-induced physiological perturbations, serological markers undergo marked changes over the course of recovery, from initial pathological levels that normalize within a year. The findings from this study are important, as they provide a benchmark for clinical decision making and prospective clinical trials. All results can be interactively explored on the Haemosurveillance web site (https://jutzelec.shinyapps.io/Haemosurveillance/) and GitHub repository (https://github.com/jutzca/Systemic-effects-of-Spinal-Cord-Injury).

Spinal cord injury as an indicator of abuse in forensic assessment of abusive head trauma (AHT).

Abusive head trauma (AHT) in children is notoriously one of the most challenging diagnoses for the forensic pathologist. The pathological "triad", a combination of intracranial subdural haematoma, cerebral oedema with hypoxic-ischaemic changes and retinal haemorrhages, is frequently argued to be insufficient to support a corroborated verdict of abuse. Data from all available English-language scientific literature involving radiological and neuropathological spinal cord examination is reviewed here in order to assess the contribution of spinal cord changes in differentiating abusive from accidental head trauma. In agreement with the statistically proven association between spinal subdural haemorrhage (SDH) and abuse (Choudhary et al. in Radiology 262:216-223, 2012), spinal blood collection proved to be the most indicative finding related to abusive aetiology. The incidence of spinal blood collection is as much as 44-48% when all the spinal cord levels are analysed as opposed to just 0-18% when the assessment is performed at cervical level only, in agreement with the evidence of the most frequent spinal SDH location at thoracolumbar rather than cervical level. In this review, the source of spinal cord blood collection and how the age of the child relates to the position of spinal cord lesions is also discussed. We concluded that the ante mortem MRI examination and post mortem examination of whole-length spinal cord is of fundamental interest for the assessment of abuse in the forensic setting.

Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis.

BACKGROUND: Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed. OBJECTIVE: We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making. METHODS: We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury. RESULTS: The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking. CONCLUSIONS: Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

Decreased angiogenesis as a possible pathomechanism in cervical degenerative myelopathy.

Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.

Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 as a Biomarker of Human Acute Traumatic Spinal Cord Injury.

A major obstacle for translational research in acute spinal cord injury (SCI) is the lack of biomarkers that can objectively stratify injury severity and predict outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that shows promise as a diagnostic biomarker in traumatic brain injury (TBI), but has not been studied in SCI. In this study, cerebrospinal fluid (CSF) and serum samples were collected over the first 72-96 h post-injury from 32 acute SCI patients who were followed prospectively to determine neurological outcomes at 6 months post-injury. UCH-L1 concentration was measured using the Quanterix Simoa platform (Quanterix, Billerica, MA) and correlated to injury severity, time, and neurological recovery. We found that CSF UCH-L1 was significantly elevated by 10- to 100-fold over laminectomy controls in an injury severity- and time-dependent manner. Twenty-four-hour post-injury CSF UCH-L1 concentrations distinguished between American Spinal Injury Association Impairment Scale (AIS) A and AIS B, and AIS A and AIS C patients in the acute setting, and predicted who would remain "motor complete" (AIS A/B) at 6 months with a sensitivity of 100% and a specificity of 86%. AIS A patients who did not improve their AIS grade at 6 months post-injury were characterized by sustained elevations in CSF UCH-L1 up to 96 h. Similarly, the failure to gain >8 points on the total motor score at 6 months post-injury was associated with higher 24-h CSF UCH-L1. Unfortunately, serum UCH-L1 levels were not informative about injury severity or outcome. In conclusion, CSF UCH-L1 in acute SCI shows promise as a biomarker to reflect injury severity and predict outcome.

MiR-665 inhibits inflammatory response in microglia following spinal cord injury by targeting TREM2.

OBJECTIVE: The purpose of this study was to uncover the role of microRNA-665 (miR-665) in protecting inflammatory response in microglia following spinal cord injury (SCI) and the underlying mechanism. PATIENTS AND METHODS: The serum levels of miR-665 and TREM2 (triggering receptor expressed on myeloid 2) in SCI patients (n=24) and healthy subjects (n=24) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). After lipopolysaccharide (LPS) induction in BV2 cells, the relative levels of miR-665 and TREM2 were detected by qRT-PCR, and relative levels of IL-6 and TNF-α in the culture medium were examined by ELISA. Next, TREM2, the target gene of miR-665, was determined by Dual-Luciferase reporter assay, and the relationship between the expression levels of TREM2 and miR-665 in SCI patients and BV2 cells was analyzed. Finally, the regulatory effects of miR-665 and TREM2 on IL-6 and TNF-α levels in the culture medium of LPS-induced BV2 cells were assessed. RESULTS: It was found that miR-665 was downregulated in serum of SCI patients and LPS-induced BV2 cells, while TREM2 was upregulated. Silenced miR-665 or overexpressed TREM2 was involved in protecting inflammatory response following SCI. Besides, rescue experiments showed that miR-665 participated in the regulation of inflammatory response following SCI by targeting TREM2. CONCLUSIONS: MiR-665 inhibits inflammatory response following SCI by targeting TREM2.

Diagnostic blood RNA profiles for human acute spinal cord injury.

Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Screening of disease-related biomarkers related to neuropathic pain (NP) after spinal cord injury (SCI).

BACKGROUND: Based on the molecular expression level, this paper compares lncRNA and mRNA expressions respectively in peripheral blood samples of the patients after SCI with NP and without NP, and screens disease-related biomarkers related to NP after SCI in peripheral blood samples of patients. METHOD: The expression spectrum of 25 human peripheral blood samples (12 samples of refractory NP patients after SCI) was downloaded and data were normalized. Screening of GO annotations significantly associated with significant differentially expressed mRNAs and significant involvement of the KEGG pathway. The WGCNA algorithm was used to screen for modules and RNAs that were significantly associated with disease characterization. A co-expression network was constructed to extract the genes involved in the disease pathway from the co-expression network, construct a network of SCI pain-related pathways, and screen important disease-related biomarkers. Quantitative real-time PCR was used to detect the mRNA expression of hub genes. RESULTS: Data were normalized and re-annotated by detection of platform information, resulting in a total of 289 lncRNA and 18197 mRNAs. Screening resulted in 338 significant differentially expressed RNAs that met the threshold requirements. Differentially expressed RNAs were significantly enriched with the brown and magenta modules. Six KEGG signaling pathways were screened in the co-expression network, and three KEGG pathways with direct neuropathic pain were identified. The expression levels of E2F1, MAX, MITF, CTNNA1, and ADORA2B in the disease group were all significantly upregulated (p < 0.01). Compared with the normal group, the expression of OXTR was upregulated. CONCLUSION: We speculate that there are 7 genes and 2 lncRNAs directly involved in the pain pathway: E2F1, MAX, MITF, CTNNA1, ADORA2B, GRIK3, OXTR, LINC01119, and LINC02447. These molecules may be important for NP after SCI.

Routinely Measured Hematological Markers Can Help to Predict American Spinal Injury Association Impairment Scale Scores after Spinal Cord Injury.

Neurological outcomes following spinal cord injury (SCI) are currently difficult to predict. While the initial American Spinal Injury Association Impairment Scale (AIS) grade can give an estimate of outcome, the high remaining degree of uncertainty has stoked recent interest in biomarkers for SCI. This study aimed to assess the prognostic value of routinely measured blood biomarkers by developing prognostic models of AIS scores at discharge and 12 months post-injury. Routine blood and clinical data were collected from SCI patients (n = 417), and blood measures that had been assessed in less than 50% of patients were excluded. Outcome neurology was obtained from AIS and Spinal Cord Independence Measure III (SCIM-III) scores at discharge and 12 months post-injury, with motor (AIS) and sensory (AIS, touch and prick) abilities being assessed individually. Linear regression models with and without elastic net penalization were created for all outcome measures. Blood measures associated with liver function, such as alanine transaminase, were found to add value to predictions of SCIM-III at discharge and 12 months post-injury. Further, components of a total blood count, including hemoglobin, were found to add value to predictions of AIS motor and sensory scores at discharge and 12 months post-injury. These findings corroborate the results of our previous preliminary study and thus provide further evidence that routine blood measures can add prognostic value in SCI and that markers of liver function are of particular interest.

Association between Serum IL-37 and Spinal Cord Injury: A Prospective Observational Study.

OBJECTIVE: Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. METHODS: All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. RESULTS: A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = -0.327, p < 0.05). CONCLUSION: The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI.