Spinal Cord Compression Injury Research Articles

Intensive Locomotor Training Provides Sustained Alleviation of Chronic Spinal Cord Injury-Associated Neuropathic Pain: A Two-Year Pre-Clinical Study.

Neuropathic pain often accompanies the functional deficits associated with spinal cord injury (SCI) and further reduces a patient's quality of life. Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol on rats that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7/8) was used and treadmill training was initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study). In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of anti-nociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest that long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.

Establishing mild, moderate and severe criteria for the myelopathy disability index in cervical spondylotic myelopathy

Aim Cervical Spondylotic Myelopathy (CSM) is a disabling condition arising from arthritic compression and consequent injury of the cervical spinal cord. Stratification of CSM severity has been useful to inform clinical practice and research analysis. In the UK the Myelopathy Disability Index (MDI) is a popular assessment tool and has been adopted by the British Spinal Registry. However, no categories of severity exist. Therefore, the aim of this study was to define categories of mild, moderate and severe. Method An anchor-based analysis was carried out on previously collected data from a prospective observational cohort (N = 404) of patients with CSM scheduled for surgery and assessed pre-operatively and at 3, 12, 24 and 60 months post-operatively. Outcomes collected included the SF-36 version-1 quality of life measure, visual analogue scales for neck/arm/hand pain, MDI and Neck Disability Index (NDI). A Receiver Operating Curve (ROC) analysis, using the NDI for an anchor-based approach, was performed to identify MDI thresholds. Results Complete data was available for 404 patients (219 Men, 185 Women). The majority of patients underwent anterior surgery (284, 70.3%). ROC curves plotted to identify the thresholds from mild to moderate to severe disease, selected optimal thresholds of 4–5 (AUC 0.83) and 8–9 (AUC 0.87). These MDI categories were validated against domains of the SF36 and VAS scores with expected positive linear correlations. Conclusion Categories of mild, moderate and severe CSM according to the MDI of 4–5 and 8–9 were established based on the NDI.

New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats.

Despite the variety of experimental models of spinal cord injury (SCI) currently used, the model of the ventral compression cord injury, which is commonly seen in humans, is very limited. Ventral balloon compression injury reflects the common anatomical mechanism of a human lesion and has the advantage of grading the injury severity by controlling the inflated volume of the balloon. In this study, ventral compression of the SCI was performed by the anterior epidural placement of the balloon of a 2F Fogarty’s catheter, via laminectomy, at the level of T10. The balloon was rapidly inflated with 10 or 15 μL of saline and rested in situ for 5 min. The severity of the lesion was assessed by behavioral and immunohistochemical tests. Compression with the volume of 15 μL resulted in severe motor and sensory deficits represented by the complete inability to move across a horizontal ladder, a final Basso, Beattie and Bresnahan (BBB) score of 7.4 and a decreased withdrawal time in the plantar test (11.6 s). Histology and immunohistochemistry revealed a significant loss of white and gray matter with a loss of motoneuron, and an increased size of astrogliosis. An inflation volume of 10 μL resulted in a mild transient deficit. There are no other balloon compression models of ventral spinal cord injury. This study provided and validated a novel, easily replicable model of the ventral compression SCI, introduced by an inflated balloon of Fogarty´s catheter. For a severe incomplete deficit, an inflated volume should be maintained at 15 μL.

Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord

BackgroundAlterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord.MethodsWe analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury.ResultsWe found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils’ population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury.ConclusionCollectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.

Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury.

Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1min) followed by intrathecal injection of vehicle or RvD3 (1μg/20μL) at 1h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.

LncRNA Xist Contributes to Endogenous Neurological Repair After Chronic Compressive Spinal Cord Injury by Promoting Angiogenesis Through the miR-32-5p/Notch-1 Axis.

Endogenous repair after chronic compressive spinal cord injury (CCSCI) is of great clinical interest. Ischemia-hypoxia-induced angiogenesis has been proposed to play an important role during this repair process. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathophysiological processes of various diseases. Here, we identified a lncRNA (Xist; X-inactive specific transcript) with upregulated expression in cervical spine lesions during endogenous neurological repair in CCSCI rats. Therapeutically, the introduction of Xist to rats increased neurological function in vivo as assayed using the Basso, Beattie, and Bresnahan (BBB) score and inclined plane test (IPT). We found that the introduction of Xist enhanced endogenous neurological repair by promoting angiogenesis and microvessel density after CCSCI, while depletion of Xist inhibited angiogenesis and cell sprouting and migration. Mechanistically, Xist promoted angiogenesis by sponging miR-32-5p and modulating Notch-1 expression both in vitro and in vivo. These findings suggest a role of the Xist/miR-32-5p/Notch-1 axis in endogenous repair and provide a potential molecular target for the treatment of ischemia-related central nervous system (CNS) diseases.

Perforin affects regeneration in a mouse spinal cord injury model

Purpose of study: To study the role of the immune response in spinal cord injury, we previously investigated the effects of genetic deletion of functional T- and B-lymphocytes in recombination activating gene 2 (Rag2)-deficient mice. To dissect out another defined and more restricted component of the immune system, we now analyzed mice deficient in perforin, an enzyme with proteolytic activity expressed mainly by natural killer and cytotoxic lymphocytes. Materials and methods Locomotor outcomes in perforin-deficient (Pfp-/-) mice and wild-type littermate controls were measured after severe compression injury of the lower thoracic spinal cord up to six weeks after injury. Results According to both the Basso mouse scale score and single frame motion analysis, motor recovery of Pfp-/- mice was similar to wild-type controls. Interestingly, immunohistochemical analysis of cell types at six weeks after injury showed enhanced cholinergic reinnervation of spinal motor neurons caudal to the lesion site and neurofilament-positive structures at the injury site in Pfp-/- mice, whereas numbers of microglia/macrophages and astrocytes were decreased compared with controls. Conclusions We conclude that, although, loss of perforin does not change the locomotor outcome after injury, it beneficially affects diverse cellular features, such as number of axons, cholinergic synapses, astrocytes and microglia/macrophages at or caudal to the lesion site. Perforin’s ability to contribute to Rag2’s influence on locomotion was observed in mice doubly deficient in perforin and Rag2 which recovered better than Rag2-/- or Pfp-/- mice, suggesting that natural killer cells can cooperate with T- and B-cells in spinal cord injury.

Inpatient rehabilitation outcomes in neoplastic spinal cord compression vs. traumatic spinal cord injury

Objective: To compare neurological and functional outcomes, and complications of patients with neoplastic vs traumatic spinal cord injury (SCI) after in-patient rehabilitation. Design: This study is a retrospective analysis. Setting: In-patient rehabilitation unit of a tertiary research hospital. Participants: A total of 252 patients with a SCI were included; 43 with neoplastic SCI (mean age: 60.9 ± 15.7 years, 60.5% were males) and 209 with traumatic SCI (mean age: 43.1 ± 16.8 years, 71.3% were males). Outcome measures: Comparisons were made of demographic characteristics, etiology, American Spinal Injury Association (ASIA) impairment scale, functional independence measurement (FIM) and Functional Ambulation Categories (FAC) scores, length of stay (LOS), bladder independence, medical comorbidities and complications in both groups. Results: Patients with neoplastic SCI were significantly older than those with traumatic SCI (P < 0.01). No difference was present between the groups in terms of sex and lesion level (P > 0.05). Incomplete SCI was significantly higher in the neoplastic group when compared with the traumatic group (P < 0.01). The LOS was significantly shorter in the neoplastic group than traumatic group (34.8 ± 41.03 vs. 60.02 ± 53.1, P < 0.01). There were no differences in the admission FIM scores (69.3 ± 24.7 vs. 58.7 ± 18.9, P > 0.05), discharge FIM scores (82.1 ± 25.1 vs. 74.02 ± 23.3, P > 0.05) and FIM efficiencies (0.43 ± 0.72 vs. 0.36 ± 0.51, P > 0.05) for the neoplastic and traumatic groups, respectively. However, neoplastic SCI patients demonstrated lower FIM gains compared to traumatic patients (12.9 ± 11.9 vs. 15.4 ± 15.2, P < 0.05). During rehabilitation, urinary tract infection (48.4% vs. 69.4%) and decubitus ulcer (11.6% vs. 35.9%) were significantly more common in the traumatic group than the neoplastic group (P < 0.05). Conclusion: Neoplastic SCI patients who commonly present at rehabilitation units exhibit different characteristics from traumatic SCI patients but the rehabilitation results are similar. Similar functional development can be achieved in a shorter period of time with inpatient rehabilitation in the neoplastic SCI group.

The effect of periaqueductal gray's metabotropic glutamate receptor subtype 8 activation on locomotor function following spinal cord injury.

Background and aims The pathophysiology of spinal cord injury is very complex. One of the debilitating aspects of spinal cord injury in addition to pain is a defect in motor function below the lesion surface. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, on animal's locomotor functions in a model of compression spinal cord injury. Methods We used a contusion method (T6-T8) for induction of spinal cord injury. Male Wistar rats were randomly assigned to five equal groups (n = 10 per group). Clips compression injury model was used to induce spinal cord injury. Three weeks post injury DCPG, siRNA (small interfering Ribonucleic Acid) and normal saline (vehicle) were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Motor function, were assessed through BBB (Basso, Beattie, and Bresnahan Locomotor Rating Scale) and ladder walking test. In addition, the effects of DCPG on axonal regeneration in corticospinal tract were evaluated. Results We found that DCPG could improve motor function and axonal regeneration in corticospinal tract when compared to siRNA group. Conclusions The results revealed that activation of mGluR8 in PAG is capable to improve motor function and of axonal regeneration due to the inhibitory effect on glutamate transmission on the spinal cord surface and also the elimination of the deleterious effect of glutamate on the regeneration of the injured area as an excitatory neurotransmitter. Implications Our findings in this study showed that, more attention should be paid to glutamate and its receptors in spinal cord injury studies, whether at the spinal or cerebral level, especially in the field of motor function after spinal cord injury.

Recovery of motricity and micturition after transplantation of mesenchymal stem cells in rats subjected to spinal cord injury

The objective was to evaluate the effect of human adipose-derived stem cell (hADSC) infusion on impaired hindlimb function and urinary continence after spinal cord contusion in rats. hADSCs were transplanted into the injured spinal cords of rats 7 and 14 days after injury in two groups (B and C). Group C also received methylprednisolone sodium succinate (MPSS) after 3 h of injury. The control group (group A) did not receive corticoids or stem cells. Voiding and motor performance evaluations were performed daily for 90 days post-transplantation. Cells were labeled with PKH26 or PKH67 for in vitro monitoring. For in vivo screening, the cells were evaluated for bioluminescence. The levels of some cytokines were quantified in different times. Euthanasia was performed 90 days post-transplant. β-tubulin III expression was evaluated in the spinal cord of the animals from all groups. As a result, we observed a recovery of 66.6 % and 61.9 % in urinary continence of animals from groups B and C, respectively. Partial recovery of motor was observed in 23.8 % and 19 % of the animals from groups B and C, respectively. Cells remained viable at the site up to 90 days after transplantation. No significant difference was observed in levels of cytokines and thickness of urinary bladders between groups. A smaller percentage of tissue injury and higher concentrations of neuropils were observed in the spinal cords of the animals from groups B and C than control group. Thus, hADSCs transplantation with or without MPSS, contributed to the improvement in voiding and motor performance of Wistar rats submitted to compressive spinal cord injury.

MiR-384-5p promotes spinal cord injury recovery in rats through suppressing of autophagy and endoplasmic reticulum stress

BackgroundSpinal cord injury (SCI) is one of the most serious neurological disorders and is characterized by high morbidity and disability. Unfortunately, there is a lack of effective treatment. Recently, the micro RNA, miR-384-5p, was reported to play a significant role in cell survival in response to different insults. MethodsIn vitro model of traumatic neuronal injury was induced by application of a sharp sterile blade to generate cuts in PC12 cells, and in vivo SCI was produced by applying vascular clips (force of 15 g) to the dura via T9–T10 laminectomy, and then, the role of miR-384-5p in the development of SCI was investigated. ResultsDual-luciferase reporter assays confirmed that miR-384-5p regulates the gene expression of Beclin-1, an important promoter of autophagy. Quantitative polymerase chain reaction and western blot analyses revealed that treatment with miR-384-5p decreased mRNA and protein expression of Beclin-1 in the mechanically injured PC12 cells. In rats with spinal cord compression injuries, miR-384-5p expression was significantly decreased. Treatment with miR-384-5p increased spinal cord neuron survival and promoted locomotor function recovery in rats. Further study revealed that miR-384-5p administration decreased immunofluorescent labeling of Beclin-1 in spinal cord tissues and reduced autophagosome formation in neurons, as shown by transmission electron microscopy. These results indicated that miR-384-5p promotes recovery of rats with SCI by suppressing autophagy via direct targeting of Beclin-1. Moreover, miR-384-5p also inhibited the activation of endoplasmic reticulum (ER) stress by decreasing GRP78 expression in both in vitro and in vivo models. ConclusionsThis study for the first time demonstrates that the protective role of miR-384-5p in the process of SCI is associated with simultaneous suppression of autophagy and ER stress and miR-384-5p could be a promising candidate for SCI therapeutics.

The effects of intrathecal ketamine on improving sensory-motor function in a rat model of compression spinal cord injury

The effects of intrathecal ketamine on improving sensory-motor function in a rat model of compression spinal cord injury

The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats

BackgroundSpinal cord injury is one of the most common causes of neuropathic pain which is not responsive to common treatments. Owing to the adverse effects of drugs, it seems that the use of Calcitonin Gene-Related Protein (CGRP) receptor antagonist or Morphine and their combination could be an appropriate strategy for pain alleviation. MethodTo achieve the objective, fifty six male Wistar rats were divided into seven groups. CGRP8-37 and Endomorphin-1 alone, and in combinated administration, as bolus and continues dose. Both mechanical and cold allodynia, and mechanical hyperalgesia were evaluated before and also15 and 60 min after injection to indicate the efficacy of the therapies in the acute and chronic circumstances on pain induced by spinal cord compression injury. Sigma-1 receptor experssion, oxidant and antioxidant activity after the seven days of the drug adminestration were evaluated. ResultThe results showed that Endomorphin-1and CGRP8-37 injections were able to reduce neuropathic pain after spinal cord compression injury. Compared to Endomorphin-1, or CGRP8-37 monotherapy, combination therapy did not show more attenuating effects on the pain threshold. Compared to the continous administration of Endomorphin-1 alone, and CGRP8-37 alone, the continous combination therapy did not reduce the pain further. Molecular studies disclosed the increased expression of the Sigma1 receptor, in the spinal cord after administration of Endomorphin-1, and CGRP8-37 alone, as well as combination therapy. Although, an increase in GPx and SOD activity, and decrease in MDA activity was observed in the combination therapy. ConclusionOur results demonstrate that either Endomorphin-1 or CGRP receptor antagonist is able to decrease the neuropathic pain after SCI but combination therapy by a CGRP receptor antagonist and Endomorphin-1 did not make any further reduction in pain sensation.

A Study of Critical Events That Lead to Spinal Cord Injury and the Importance of Rapid Reversal of Surgical Steps in Improving Neurological Outcomes: A Porcine Model.

Porcine model. To quantify critical vascular and mechanical events that occur before and during an evolving spinal cord injury. Spinal cord injuries are one of the most devastating complications in spine surgery. Intraoperative neuromonitoring changes can occur as a secondary event of spinal cord compression and decrease in spinal cord blood flow (SCBF). Laser Doppler flowmetry has been well validated for measuring blood flow. Seventeen pigs were studied, 14 of which completed the experiment. Multilevel, midthoracic laminectomies were performed. Laser Doppler flowmetry electrodes were placed on the dura to measure SCBF. Spinal cord injury was induced by incremental balloon inflation in the epidural space. The animals were separated into two groups. After motor-evoked potential (MEP) loss, group A underwent medical interventions and then balloon decompression approximately 20 minutes later. Group B underwent immediate balloon decompression followed by medical interventions. After interventions, wake-up test was performed and computed tomography scan measured thoracic spinal canal volume. Median SCBF changes were seen 15.8 (5.4-25.1) minutes before MEP loss. However, the 20% threshold interval was often reached before. At the 20% threshold, median pressure was 7 psi, balloon volume was 0.5 cm, and 50% of the spinal canal was compromised. In group A, no pigs moved and all had pathology indicating ischemia. In group B, 9 of 10 were found to be moving their hind legs with 7 indicating ischemia. Compression spinal cord injury is the end of a cascade involving increasing intracanal pressure, decreasing canal volume, and hypoperfusion. Rapid relief of compression leads to MEP return. SCBF monitoring can detect ischemia preinjury, giving surgeons an opportunity for early intervention. 4.

The repair and autophagy mechanisms of hypoxia-regulated bFGF-modified primary embryonic neural stem cells in spinal cord injury.

There is no effective strategy for the treatment of spinal cord injury (SCI), a devastating condition characterized by severe hypoxia and ischemic insults. In this study, we investigated the histology and pathophysiology of the SCI milieu in a rat model and found that areas of hypoxia were unevenly interspersed in compressed SCI. With this new knowledge, we generated embryonic neural stem cells (NSCs) expressing basic fibroblast growth factor (bFGF) under the regulation of five hypoxia‐responsive elements (5HRE) using a lentiviral vector (LV‐5HRE‐bFGF‐NSCs) to specifically target these hypoxic loci. SCI models treated with bFGF expressed by the LV‐5HRE‐bFGF‐NSCs viral vector demonstrated improved recovery, increased neuronal survival, and inhibited autophagy in spinal cord lesions in the rat model due to the reversal of hypoxic conditions at day 42 after injury. Furthermore, improved functional restoration of SCI with neuron regeneration was achieved in vivo, accompanied by glial scar inhibition and the evidence of axon regeneration across the scar boundary. This is the first study to illustrate the presence of hypoxic clusters throughout the injury site of compressed SCI and the first to show that the transplantation of LV‐5HRE‐bFGF‐NSCs to target this hypoxic microenvironment enhanced the recovery of neurological function after SCI in rats; LV‐5HRE‐bFGF‐NSCs may therefore be a good candidate to evaluate cellular SCI therapy in humans.

5-Nonyloxytryptamine oxalate-embedded collagen-laminin scaffolds augment functional recovery after spinal cord injury in mice.

Polysialic acid (PSA) is crucial for the induction and maintenance of nervous system plasticity and repair after injury. In order to exploit the immense therapeutic potential of PSA, previous studies have focused on the identification and development of peptide-based or synthetic PSA mimetics. 5-Nonyloxytryptamine (5-NOT) has been previously reported as a PSA-mimicking compound for promoting functional recovery after spinal cord injury in mice. In order to explore the neuroregeneration potential of 5-NOT, the current study was based on a biomaterial approach using collagen-laminin (C/L) scaffolds. In in vitro studies, 5-NOT was observed to promote neurite outgrowth, migration, and fasciculation in cerebellar neuronal cells, whereas in 3D cell cultures it showed more ramification and complex Sholl profiles. 5-NOT promoted the survival and neurite length of cortical neurons when cocultured with glutamate-challenged astrocytes. In in vivo studies, spinal cord compression injury mice were used with immediate application of C/L hydrogels impregnated with 5-NOT. C/L + 5-NOT-treated mice demonstrated ∼75% of motor recovery 14 days after injury. Furthermore, this effect was shown to be dependent on the ERK-MAPK pathway and augmentation of cell survival. Thus, based on a biomaterial approach, our current study provides new insight for 5-NOT-containing hydrogels as a promising candidate to speed up recovery after central nervous system injuries.

Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord

The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti-inflammatory cells that restrain post-SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up-regulated in infiltrating Treg cells. Using lentivirus-mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin-10, and transforming growth factor-β in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide-stimulated spinal cord CD11b+ myeloid cells. Knock-down of SIRT4 enhanced the anti-inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down-regulated 5' AMP-activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin-10 in SIRT4-overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post-SCI neuroinflammation is regulated.

Exploration of Cervical Myelopathy Location From Somatosensory Evoked Potentials Using Random Forests Classification.

Studies using time-frequency analysis have reported that somatosensory evoked potentials provide information regarding the location of spinal cord injury. However, a better understanding of the time-frequency components derived from somatosensory evoked potentials is essential for developing more reliable algorithms that can diagnosis level (location) of cervical injury. In the present study, we proposed a random forests machine learning approach, for separating somatosensory evoked potentials depending on spinal cord state. For data acquisition, we established rat models of compression spinal cord injury at the C4, C5, and C6 levels to induce cervical myelopathy. After making the compression injury, we collected somatosensory evoked potentials and extracted their time-frequency components. We then used the random forests classification system to analyze the evoked potential dataset that was obtained from the three groups of model rats. Evaluation of the classifier performance revealed an overall classification accuracy of 84.72%, confirming that the random forests method was able to separate the time-frequency components of somatosensory evoked potentials from rats under different conditions. Features of the time-frequency components contained information that could identify the location of the cervical spinal cord injury, demonstrating the potential benefits of using time-frequency components of somatosensory evoked potentials to diagnose the level of cervical injury in cervical myelopathy.

Gall stone pancreatitis in a syringomyelia patient: case report and historical review

Syringomyelia is a rare neurological disorder generally regarded as chronic, characterized by slowly progressing fluid-filled cyst (syrinx) forms within the spinal cord. Here we describe the historical review of a patient suffering from syringomyelia for the past 16 years and present gastric condition- gall stone induced pancreatitis. A quadriparetic female patient who had previously undergone surgical treatment for syringomyelia with the early signs including muscle weakness and wasting (atrophy), loss of reflexes, loss of sensitivity to pain and temperature and also stiffness in back, shoulders, spinal curvature (scoliosis) presenting complains of multiple episodes of hematemesis and severe constipation since 5 days. Ultrasonography imaging and laboratory investigations revealed gallbladder stone induced acute pancreatitis also associated. The patient underwent multiple surgical interventions for syrinx removal and associated surgical complications were managed adequately. Currently, the pancreatitis was managed by laparoscopic corrections. Postoperatively, there was a prompt resolution of pancreatitis and associated gastric symptoms. In conclusion, early diagnosis of syringomyelia with magnetic resonance imaging is critical in the prophylaxis of spinal cord compression and potential neurologic injury. Surgical interventions are recommended in symptomatic cases. This case report describes clinical manifestations and management of acute pancreatitis in a chronic sufferer of syringomyelia.

A novel spinal cord surrogate for the study of compressive traumatic spinal cord injuries.

Although in vitro studies are frequent for the study of traumatic spine and spinal cord injuries, few include the spinal cord due to its prompt post-mortem decay. Several materials have been proposed to mimic the spinal cord behaviour, but none matched its mechanical properties under transverse compression, which is vital for the study of burst fractures and other injury mechanisms leading to spinal cord compression. In this study, a new material named Soma Foama 15 (Reynolds Advanced Material, USA) was used to manufacture three spinal cord surrogates at 3 mixing ratios of elastomer to catalyst (1:1, 2:1 and 3:1) and tested at three different strain rates (0.5, 5 and 50 .s-1). The mixing ratio 3:1 presents a mechanical behaviour comparable to that of the porcine spinal cord at each of these strain rates, making the surrogate a valid substitute up to 75 % of transverse compression.