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.

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.

Selenium and copper status - potential signposts for neurological remission after traumatic spinal cord injury.

INTRODUCTION: Traumatic Spinal Cord Injury (TSCI) is a severe incident resulting in loss of motor and sensory function caused by complex pathological mechanisms including massive oxidative stress and extensive inflammatory processes. The essential trace elements selenium (Se) and copper (Cu) play crucial roles as part of the antioxidant defense. HYPOTHESIS: Remission after TSCI is associated with characteristic dynamics of early changes in serum Cu and Se status. STUDY DESIGN: Single-center prospective observational study. PATIENTS AND METHODS: Serum samples from TSCI patients were analyzed (n = 52); 21 recovered and showed a positive abbreviated injury score (AIS) conversion within 3 months (G1), whereas 21 had no remission (G0). Ten subjects with vertebral fractures without neurological impairment served as control (C). Different time points (at admission, and after 4, 9, 12, and 24 h) were analyzed for total serum Se and Cu concentrations by total reflection X-ray fluorescence, and for Selenoprotein P (SELENOP) and Ceruloplasmin (CP) by sandwich ELISA. RESULTS: At admission, CP and SELENOP concentrations were higher in the remission group (G1) than in the non-remission group (G0). Within 24 h, there were marginal changes in Se, SELENOP, Cu and CP concentrations in the groups of controls (C) and G0. In contrast, these parameters decreased significantly in G1. Binary logistic regression analysis including Cu and Se levels at admission in combination with Se and CP levels after 24 h allowed a prediction for potential remission, with an area under the curve (AUC) of 87.7% (CI: 75.1%-100.0%). CONCLUSION: These data indicate a strong association between temporal changes of the Se and Cu status and the clinical outcome after TSCI. The dynamics observed may reflect an ongoing redistribution of the trace elements in favor of a better anti-inflammatory response and a more successful neurological regeneration.

Skeletal muscle hypertrophy and attenuation of cardio-metabolic risk factors (SHARC) using functional electrical stimulation-lower extremity cycling in persons with spinal cord injury: study protocol for a randomized clinical trial.

BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.

Comparative pharmacokinetic study on phenolic acids and flavonoids in spinal cord injury rats plasma by UPLC-MS/MS after single and combined oral administration of danshen and huangqin extract.

Chinese medicinal herbs danshen and huangqin have attracted attention in spinal cord injury (SCI) treatment. Purpose of this study was to investigate and compare the pharmacokinetic characteristics of 4 phenolic acids and 4 flavonoids in SCI rat plasma after orally administrate danshen, huangqin and combined extract of these two herbs (CDH). Thus, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously quantitative determination of tanshinol, protocatechualdehyde, protocatechuic acid, salvianolic acid A, baicalein, baicalin, wogonin and wogonoside. After inducing a contusion injury by a weight-drop device, SCI rats were orally administrated a single dose (12.5 g/kg) of danshen, huangqin and CDH extracts, respectively. Then, blood samples at different time points were collected and analyzed. In CDH group, Cmax and AUC of tanshinol, protocatechualdehyde and protocatechuic acid significantly declined, while those of salvianolic acid A enhanced. These changes were beneficial for danshen to treat SCI. As for flavonoids, double peaks were observed in huangqin group, while this phenomenon disappeared in CDH group. Concomitantly, Cmax and AUC declined after administrated CDH. These alterations were due to influence of danshen active constituents on absorption and transportation process of flavonoids. Therefore, danshen and huangqin significantly influenced pharmacokinetic profile and parameters of each other, thus exert synergistic therapeutic effect in SCI treatment.

Relation of selenium status to neuro-regeneration after traumatic spinal cord injury.

INTRODUCTION: The trace element selenium (Se) is crucial for the biosynthesis of selenoproteins. Both neurodevelopment and the survival of neurons that are subject to stress depend on a regular selenoprotein biosynthesis and sufficient Se supply by selenoprotein P (SELENOP). HYPOTHESIS: Neuro-regeneration after traumatic spinal cord injury (TSCI) is related to the Se status. STUDY DESIGN: Single-centre prospective observational study. PATIENTS AND METHODS: Three groups of patients with comparable injuries were studied; vertebral fractures without neurological impairment (n = 10, group C), patients with TSCI showing no remission (n = 9, group G0), and patients with remission developing positive abbreviated injury score (AIS) conversion within 3 months (n = 10, group G1). Serum samples were available from different time points (upon admission, and after 4, 9 and 12 h, 1 and 3 days, 1 and 2 weeks, and 1, 2 and 3 months). Serum trace element concentrations were determined by total reflection X-ray fluorescence, SELENOP by ELISA, and further parameters by laboratory routine. RESULTS: Serum Se and SELENOP concentrations were higher on admission in the remission group (G1) as compared to G0. During the first week, both parameters remained constant in C and G0, whereas they declined significantly in the remission group. Similarly, the concentration changes between admission and 24 h were most pronounced in this group of recovering patients (G1). Binary logistic regression analysis including the delta of Se and SELENOP within the first 24 h indicated an AUC of 90.0% (CI: 67.4%-100.0%) with regards to predicting the outcome after TSCI. CONCLUSION: A Se deficit might constitute a risk factor for poor outcome after TSCI. A dynamic decline of serum Se and SELENOP concentrations after admission may reflect ongoing repair processes that are associated with higher odds for a positive clinical outcome.

Effect of hyperbaric oxygen therapy on HMGB1/NF-κB expression and prognosis of acute spinal cord injury: A randomized clinical trial.

Although there are reports of the beneficial effects of hyperbaric oxygen (HBO) therapy in experimental settings, there are few clinical trials of HBO therapy for acute spinal cord injury (SCI). We investigated the effect of HBO in acute SCI by measuring plasma high mobility group box 1 (HMGB1) and nuclear factor kappa-B (NF-κB) levels, and by monitoring changes in electromyogram F-persistence (the percentage of discernible F-waves) and F-chronodispersion (the difference between minimal and maximal latency). We enrolled 79 acute SCI patients and randomly divided them into control (conventional treatment) and the treatment (conventional treatment plus HBO therapy) groups. Plasma was collected before treatment and after treatment on 1st, 3rd, 7th, 10th and 30th day for the measurement of HMGB1 and NF-κB. Electromyogram F-waves were detected before therapy and after therapy on the 10th and 30th days. Clinical profiles and neurological outcomes were evaluated using American Spinal Injury Association (ASIA) and Frankel Grade scores. Compared to the control group, HBO therapy down-regulated HMGB1 and NF-κB expression in patients with acute SCI on days 3, 7, 10 and 30 (p < 0.05). F-wave chronodispersion decreased at days 10 and 30 (p < 0.01) following HBO. ASIA and Frankel Grade motor/pain scores in the treatment group were significantly improved on day 30 (p < 0.01). There was a positive correlation between plasma NF-κB at day 7 and F-wave dispersion at day 30 (r = 0.76, p = 0.00). In summary, HBO therapy regulated the inflammatory reaction in secondary SCI by decreasing plasma HMGB1/NF-κB levels and reducing the dispersion of electromyogram F-waves of the lower limbs, thereby promoting neurological function recovery.

Changes in nutrient intake and inflammation following an anti-inflammatory diet in spinal cord injury.

Objective: The objective of the current study was to describe the observed changes in nutrient intakes following a 3-month anti-inflammatory diet, and to explore potential relationships between the change in nutrients and the change in various inflammatory mediators.Design: A secondary analysis of a prior randomized controlled clinical trial.Setting: Individuals with SCI within the Niagara region.Participants: Twenty individuals with various levels and severities of SCI.Intervention: Three-month anti-inflammatory diet.Outcome Measures: The change in nutrient intake and corresponding changes to various inflammatory mediators.Results: The treatment group demonstrated a significant reduction in fat intake (P = 0.02), a significant increase in protein intake (P = 0.02), and no change in carbohydrates (P = 0.23) or energy intake (P = 0.10). The treatment group showed a significant increase in some nutrients with established anti-inflammatory properties including vitamins A, C, and E, and omega-3 fatty acids (P < 0.01). Significant reductions in proinflammatory nutrients were observed including trans fatty acids (P = 0.05), caffeine (P < 0.01), and sodium (P = 0.02). The treatment group also showed significant reductions in the proinflammatory mediators interferon-y (P = 0.01), interleukin-1ß (P < 0.01), and interleukin-6 (P < 0.05). Further, several proinflammatory mediators were negatively correlated with anti-inflammatory nutrients, including vitamin A, carotenoids, omega-3 fatty acids, and zinc.Conclusion: This study provides evidence that dietary alterations are effective at reducing chronic inflammation in individuals with SCI and provides a preliminary assessment of the related nutrient changes.

Vitamin D, diet, and lifestyle in a chronic SCI population.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine dietary, lifestyle, and clinical factors associated with plasma 25-hydroxyvitamin D [25(OH)D] levels in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA. METHODS: 174 participants completed food frequency and health questionnaires, provided a blood sample, and underwent dual x-ray absorptiometry (DXA) to assess %total body fat. Linear regression models were used to assess cross-sectional associations of personal, lifestyle, and nutritional factors with plasma 25(OH)D. RESULTS: Independent factors positively associated with higher plasma 25(OH)D included vitamin D intake, age, hours of planned exercise, female sex, white race, wine consumption, and if a never or former smoker. The most important predictor of 25(OH)D was supplement intake. The majority of subjects (98.9% for vitamin D and 74.1% for calcium) did not meet the recommended daily allowance for adults from their diet alone. Level and completeness of SCI, injury duration, mobility, %total body fat, time outside, and comorbid diseases were not associated with plasma 25(OH)D. CONCLUSIONS: Plasma 25(OH)D level in chronic SCI is not associated with clinical factors specific to SCI such as injury level and completeness, injury duration, and mobility mode, but related to supplement intake and other lifestyle factors.

Effect of Vitamin D Supplementation on 25(OH)D Status in Elite Athletes With Spinal Cord Injury.

Recent studies suggest that a substantial proportion of athletes with spinal cord injury have insufficient 25(OH) vitamin D (25(OH)D) status, which may be associated with decreased muscle strength. This study consisted of two parts: (a) to examine the effects of a 12- to 16-week vitamin D3 supplementation protocol on 25(OH)D concentration and (b) to determine whether subsequent 25(OH)D status impacts muscle performance in elite athletes with spinal cord injury. Thirty-four members (age: 33 ± 15 years, weight: 69.6 ± 28.2 kg, and height: 170.2 ± 25.4 cm) of the U.S. and Canadian Paralympic program participated in the study. 25(OH)D concentrations and performance measures (handgrip strength and 20-m wheelchair sprint) were assessed pre- and postsupplementation. Participants were assigned a vitamin D3 supplementation protocol based on initial 25(OH)D concentrations. Participants with deficient 25(OH)D status (<50 nmol/L) received 50,000 IU/week for 8 weeks, and participants with insufficient status (50-75 nmol/L) received 35,000 IU/week for 4 weeks, after which both received a maintenance dose of 15,000 IU/week. Participants with sufficient status (>75 nmol/L) received the maintenance dose of 15,000 IU/week. 25(OH)D concentrations increased significantly (p < .001; 66.3 ± 24.3 nmol/L and 111.3 ± 30.8 nmol/L pre- and postsupplementation, respectively). About 26% of athletes had sufficient 25(OH)D concentrations presupplementation, and 91% had sufficient concentrations postsupplementation. About 62% of participants improved handgrip strength postsupplementation with no change in 20-m wheelchair sprint performance. The supplementation protocol was effective for achieving sufficient vitamin D concentrations in elite athletes with spinal cord injury.

Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation, Blood Cell Count, and IGF-1 Levels in Spinal Cord Injury-Induced Rats.

Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective effect of the oral administration of selenium nanoparticles in rats with spinal cord injury (SCI). Forty adult female rats were randomly assigned to two equal groups as experimental and control. Under general inhalation anesthesia, in both groups, SCI was created, at the T9-10 level of the column. On the third day after the operation, a supplement of selenium nanoparticle was administered to the experimental group at 0.2 mg/kg per day. The histology of the site of injury, IGF-1 serum concentrations, and changes in the white blood cells were examined in both groups at different pre-surgical and post-surgical times. The results of the current study showed a significant decrease in the total white blood cells, including lymphocyte, neutrophil, and monocyte in the experimental group compared to the control group. Histological evaluation showed that the inflammatory responses reduced significantly in the experimental group compared to the control group. In conclusion, we speculate that the decrease in the number of inflammatory cells after oral administration of the selenium nanoparticles is due to the neuroprotective effects of this nanoparticle.

Venous Thromboembolism is Associated With Lack of Vitamin D Supplementation in Patients With Spinal Cord Injury and Low Vitamin D Levels.

BACKGROUND: The role of vitamin D in the pathogenesis of venous thromboembolism (VTE) and prevalence of low vitamin D (LVitD) in spinal cord injury (SCI) has motivated vitamin D testing and supplementation. This is an exploratory study of data collected at a time before the routine clinical practice of vitamin D supplementation, allowing for evaluation of the natural history of vitamin D levels in patients with SCI. OBJECTIVE: To determine if vitamin D supplementation in persons with SCI and LVitD levels is associated with decreased prevalence of VTE. DESIGN: Retrospective cohort study. SETTING: Rehabilitation Center at a Level I Trauma Center. PARTICIPANTS: Patients with SCI admitted to acute inpatient rehabilitation (N = 282). MAIN OUTCOME MEASURES: VTE prevalence in patients with LVitD levels, grouped by presence or absence of vitamin D supplementation. RESULTS: Of the acute inpatient SCI population, 80% (227/282) of patients demonstrated vitamin D levels <30 ng/mL (LVitD). Although the incidence of VTE was almost double in the LVitD group, 19% (43/227) of the patients in the LVitD group had VTE versus 9% (5/55) of patients with vitamin D levels ≥30 ng/mL (normal VitD [NVitD]); this difference was not statistically significant (P = .108, Cramer's V = .104). When the role of vitamin D supplementation was analyzed, individuals in the LVitD group who received no vitamin D supplementation (LVitDSuppNegative) had a higher incidence of VTE (statistically significant) compared to the LVitD group with vitamin D supplementation (LVitDSuppPositive) (24% [42/178] vs. 2% [1/49]) (P < .001, Cramer's V = .226). In post hoc exploratory analyses, the VTE rate of patients in the LVitDSuppNegative group was noted to be significantly higher than that in all other patient groups combined (P < .001, Cramer's V = .229). A binary logistic regression model incorporating clinical covariates also showed this grouping to be significant. CONCLUSION: A significant association appears to exist between lack of vitamin D supplementation and VTE occurrence in persons with acute SCI and LVitD levels. LEVEL OF EVIDENCE: III.

Anti-inflammatory effect of Mongolian drug Naru-3 on traumatic spinal cord injury and its mechanism of action.

Objective This study was performed to confirm the anti-inflammatory effect of the Mongolian drug Naru-3 on traumatic spinal cord injury (TSCI) and its possible mechanism of action. Methods We prepared a TSCI model using Sprague-Dawley rats. The rats were divided into a Naru-3 group and a methylprednisolone group. Real-time polymerase chain reaction and western blotting were performed to measure the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Enzyme-linked immunosorbent assay kits were employed to detect serum inflammatory cytokine levels. The localization and expression of monocyte chemotactic protein-1 (MCP-1) in spinal cord tissue was determined by immunohistochemical analysis. Flow cytometry was performed to analyze the ratio of M1- and M2-phenotype macrophages. The locomotor function recovery was evaluated by the Basso, Beattie, and Bresnahan score. Results Naru-3 significantly inhibited the inflammatory response and reduced the expression of TNF-α, IL-6, and IL-1ß in both spinal cord and blood in a time- and concentration-dependent manner. Immunohistochemical analysis indicated that Naru-3 significantly reduced MCP-1 expression in spinal cord and promoted M2-phenotype macrophage differentiation. Conclusions Naru-3 is an effective treatment for impact-induced TSCI in rats. Naru-3 treatment affects inflammatory cytokine levels and macrophage differentiation, which play a role in TSCI remission.

Higher dietary intake of vitamin D may influence total cholesterol and carbohydrate profile independent of body composition in men with Chronic Spinal Cord Injury.

STUDY DESIGN: A case-control design. OBJECTIVES: To determine the effects of dietary vitamin D intake on insulin sensitivity (Si), glucose effectiveness (Sg), and lipid profile in individuals with spinal cord injury (SCI). METHODS: 20 male, paraplegic (T3-L1) with chronic (> one year) motor complete SCI (AIS A or B) were recruited. Three-day dietary records were analyzed for dietary vitamin D (calciferol), and participants were assigned to one of two groups, a high vitamin D intake group and a low vitamin D intake group based on the mid-point of vitamin D frequency distribution. Individuals in both groups were matched based on age, weight, time since injury and level of injury. Sg, Si and lipid profiles were measured of the two groups. RESULTS: The high vitamin D group had an average intake of 5.33 ± 4.14 mcg compared to low vitamin D group, 0.74 ± 0.24 mcg. None of the 20 participants met the recommended guidelines for daily vitamin D intake. The higher vitamin D group had a significantly lower (P = 0.035) total cholesterol (148.00 ± 14.12 mg/dl) than the lower vitamin D group (171.80 ± 36.22 mg/dl). Vitamin D adjusted to total dietary intake was positively correlated to improvement in Si and Sg (P<0.05). CONCLUSION: The findings suggest that persons with SCI consume much less than the recommended guidelines for daily vitamin D intake. However, a higher dietary intake of vitamin D may influence total cholesterol and carbohydrate profile as demonstrated by a significant decrease in total cholesterol and improvement in glucose homeostasis independent of body composition changes after SCI.

Vitamin D deficiency in individuals with a spinal cord injury: a literature review.

STUDY DESIGN: Literature review of studies investigating vitamin D status in individuals with a spinal cord injury (SCI). OBJECTIVES: Prevalence of vitamin D deficiency seems to be high in the general population. Little is known regarding such a deficiency in individuals with a SCI. This review aimed to examine the literature that investigated vitamin D status in this population. SETTING: Switzerland. METHODS: A literature review was performed to investigate the prevalence of vitamin D deficiency in individuals with a SCI and to determine the factors leading to deficiency. RESULTS: Sixteen studies which met all the inclusion criteria were identified. All of these studies assessed total serum 25-hydroxy vitamin D status in individuals with an acute or chronic SCI. Overall, the prevalence of vitamin D deficiency or insufficiency seems to be high (range: 32-93%) in this population compared with that in able-bodied persons. The main factors are immobility, low physical activity and bedrest, and therefore not enough exposure to sunlight. In addition, age, skin pigmentation, lesion level, occurrence of pressure ulcers, body mass index, season and latitude appeared to be further determinants for vitamin D deficiency. In athletes, playing their sport indoors or outdoors may have an additional role in developing vitamin D deficiency. CONCLUSION: The available studies suggest that individuals with a SCI are at increased risk for vitamin D insufficiency/deficiency. Nutritional strategies and supplementation recommendations need to be developed to prevent these conditions in SCI. SPONSORSHIP: Not applicable.

Effect of 12-Week Vitamin D Supplementation on 25[OH]D Status and Performance in Athletes with a Spinal Cord Injury.

(1) BACKGROUND: studies with able-bodied athletes showed that performance might possibly be influenced by vitamin D status. Vitamin D seems to have a direct impact on neuromuscular function by docking on vitamin D receptors in the muscle tissue. Additionally, a high prevalence of vitamin D deficiency was shown not only in infants and in the elderly but also in healthy adults and spinal cord injured individuals. Therefore, the aim of our study was to investigate whether a vitamin D dose of 6000 IU daily over 12 weeks would be sufficient to increase vitamin D status in indoor wheelchair athletes to a normal or optimal vitamin D level and whether vitamin D deficiency is associated with an impairment in muscle performance in these individuals; (2) METHODS: vitamin D status was assessed in indoor elite wheelchair athletes in order to have a baseline measurement. If vitamin D status was below 75 nmol/L, athletes were supplemented with 6000 IU of vitamin D daily over 12 weeks. A vitamin D status over 75 nmol/L was supplemented with a placebo supplement. Vitamin D status, as well as a Wingate test and an isokinetic dynamometer test, were performed at baseline and after six and 12 weeks; (3) RESULTS: 20 indoor elite wheelchair athletes participated in this double-blind study. All of these athletes showed an insufficient vitamin D status at baseline and were, therefore, supplemented with vitamin D. All athletes increased vitamin D status significantly over 12 weeks and reached an optimal level. Wingate performance was not significantly increased. Isokinetic dynamometer strength was significantly increased but only in the non-dominant arm in isometric and concentric elbow flexion; (4) CONCLUSION: a dose of 6000 IU of vitamin D daily over a duration of 12 weeks seems to be sufficient to increase vitamin D status to an optimal level in indoor wheelchair athletes. It remains unclear, whether upper body performance or muscle strength and vitamin D status are associated with each other.

25(OH)D Status of Elite Athletes with Spinal Cord Injury Relative to Lifestyle Factors.

BACKGROUND: Due to the potential negative impact of low Vitamin D status on performance-related factors and the higher risk of low Vitamin D status in Spinal Cord Injury (SCI) population, research is warranted to determine whether elite athletes with SCI have sufficient 25(OH)D levels. The purposes of this study were to examine: (1) the seasonal proportion of vitamin D insufficiency among elite athletes with SCI; and (2) to determine whether lifestyle factors, SCI lesion level, and muscle performance/function are related to vitamin D status in athletes with SCI. METHODS: Thirty-nine members of the Canadian Wheelchair Sports Association, and the US Olympic Committee Paralympic program from outdoor and indoor sports were recruited for this study. Dietary and lifestyle factors, and serum 25(OH)D concentrations were assessed during the autumn (October) and winter (February/March). An independent t-test was used to assess differences in 25(OH)D status among seasons, and indoor and outdoor sports in the autumn and winter, respectively. RESULTS: Mean ± SD serum 25(OH)D concentration was 69.6 ± 19.7 nmol/L (range from 30 to 107.3 nmol/L) and 67.4 ± 25.5 nmol/L (range from 20 to 117.3 nmol/L)in the autumn and winter, respectively. In the autumn, 15.4% of participants were considered vitamin D deficient (25(OH)D < 50 nmol/L) whereas 51.3% had 25(OH)D concentrations that would be considered insufficient (<80 nmol/L). In the winter, 15.4% were deficient while 41% of all participants were considered vitamin D insufficient. CONCLUSION: A substantial proportion of elite athletes with SCI have insufficient (41%-51%) and deficient (15.4%) 25(OH)D status in the autumn and winter. Furthermore, a seasonal decline in vitamin D status was not observed in the current study.

Vitamin D profile of patients with spinal cord injury and post-stroke hemiplegia: All in the same boat.

BACKGROUND: Patients with spinal cord injury (SCI) and hemiplegia are at risk of fractures partly due to decreased bone mineral density with relation to the low levels of vitamin D. OBJECTIVE: The objective of this study is to evaluate the vitamin D profile of patients with SCI and post-stroke hemiplegia. METHODS: 25(OH)D levels of patients with SCI and hemiplegia were obtained from the electronic medical record database and compared with age- and sex-matched non-disabled controls. Furthermore, the effect of Functional Ambulation Category (FAC), American Spinal Injury Association (ASIA) level and Brunnstrom's recovery stage, on vitamin D insufficiency, was studied. RESULTS: The study sample consisted of 173 individuals (118 patients and 55 controls). Vitamin D levels and sufficiency rates of the neurologically disabled patients was significantly lower than that of controls (p= 0.000 and p= 0.000, respectively). However, there was no difference between patients with SCI and hemiplegia regarding the 25(OH)D levels and vitamin D insufficiency (p= 0.303 and p= 0.952, respectively). There were no statistically significant differences in vitamin D status by American Spinal Injury Association (ASIA) level and Brunnstrom's score. However, regression analysis revealed that vitamin D insufficiency rate of non-functionally ambulatory (FAC = 0-2) patients was higher than that of functionally ambulatory (FAC = 3-5) ones (p= 0.044). CONCLUSIONS: Vitamin D status of patients with neurological disabilities was lower than that of controls. Non-functionally ambulatory patients had higher vitamin D insufficiency rate than functionally ambulatory patients. Preventative measures including adequate supplementation of vitamin D should be directed to neurologically disabled subjects, particularly those with non-functional ambulation.

Preliminary results of using ALAnerv® in subacute motor incomplete paraplegics.

RATIONALE: To assess whether using ALAnerv® contributes to improvements of outcomes obtained in post SCI patients. OBJECTIVE: A prospective controlled clinical survey also to evaluate the safety and efficacy of ALAnerv® (2cps/ day for 28 days) in motor incomplete (AIS/ Frankel C) paraplegic subacute patients. METHODS AND RESULTS: 59 patients divided in study (treated with ALAnerv®) and control, groups. This survey's follow-up duration was of 28 days. Most of the studied patients were mid-aged (mean 43.75 years old) and respectively, men (64,29% in the study group; 58,06% in controls). We used descriptive statistics (functions: minimum, maximum, mean, median, standard deviation) and for related comparisons, parametric (Student t) and non-parametric (Mann-Whitney, Fisher's exact, chi-square) tests. The primary end-point: AIS motor values' evolution (P= 0.015 - Mann-Whitney), showed that patients treated with ALAnerv® - vs. controls - had a statistically significant better increase of such scores at discharge. Paraclinical parameters, mainly exploring systemic inflammatory status (secondary end-point): ESR dynamics (P=0.13) had no statistical significance; the plasma leucocytes number (P=0.018), the neutrophils' percentage (P=0.001) and fibrinogenemia (P= 0,017) proved in the treated group to have a statistically significant better evolution. We used "Statistical Package for Social Sciences" (SPSS). DISCUSSION: As there is actually no effective curative solution for the devastating pathology following SCI, any medical approach susceptible to bring even limited improvements, such as treatment with ALAnerv® seemed to have proven, is worth being surveyed, under strict circumstances of ethics and research methodology. Considering the necessity for more statistical power concerning primary, secondary end-points, and safety issues, as well, continuing this research is needed. ABBREVIATIONS: SCI = spinal cord injury, TSCI = traumatic spinal cord injury, BBB = blood brain barrier, CNS = central nervous system, SC = spinal cord, NSAIDs = non-steroidal anti-inflammatory drugs, SAIDs = steroidal anti-inflammatory drugs, AIS = American Spinal Injury Association Impairment Scale, SPSS = Statistical Package for Social Sciences, BATEH = Bagdasar-Arseni Teaching Emergency Hospital.

Nanowired Delivery of Growth Hormone Attenuates Pathophysiology of Spinal Cord Injury and Enhances Insulin-Like Growth Factor-1 Concentration in the Plasma and the Spinal Cord.

Previous studies from our laboratory showed that topical application of growth hormone (GH) induced neuroprotection 5 h after spinal cord injury (SCI) in a rat model. Since nanodelivery of drugs exerts superior neuroprotective effects, a possibility exists that nanodelivery of GH will induce long-term neuroprotection after a focal SCI. SCI induces GH deficiency that is coupled with insulin-like growth factor-1 (IGF-1) reduction in the plasma. Thus, an exogenous supplement of GH in SCI may enhance the IGF-1 levels in the cord and induce neuroprotection. In the present investigation, we delivered TiO2-nanowired growth hormone (NWGH) after a longitudinal incision of the right dorsal horn at the T10-11 segments in anesthetized rats and compared the results with normal GH therapy on IGF-1 and GH contents in the plasma and in the cord in relation to blood-spinal cord barrier (BSCB) disruption, edema formation, and neuronal injuries. Our results showed a progressive decline in IGF-1 and GH contents in the plasma and the T9 and T12 segments of the cord 12 and 24 h after SCI. Marked increase in the BSCB breakdown, as revealed by extravasation of Evans blue and radioiodine, was seen at these time points after SCI in association with edema and neuronal injuries. Administration of NWGH markedly enhanced the IGF-1 levels and GH contents in plasma and cord after SCI, whereas normal GH was unable to enhance IGF-1 or GH levels 12 or 24 h after SCI. Interestingly, NWGH was also able to reduce BSCB disruption, edema formation, and neuronal injuries after trauma. On the other hand, normal GH was ineffective on these parameters at all time points examined. Taken together, our results are the first to demonstrate that NWGH is quite effective in enhancing IGF-1 and GH levels in the cord and plasma that may be crucial in reducing pathophysiology of SCI.