Biomarkers Of Spinal Cord Injury Research Articles

Potential Molecular Mechanism and Biomarker Investigation for Spinal Cord Injury Based on Bioinformatics Analysis

This study aimed to explore the detailed molecular mechanism and biomarkers in spinal cord injury (SCI). Gene expression profiles of GSE125630 were downloaded from the Gene Expression Omnibus (GEO) database, and comprised 14 spinal cord tissues, including contusion SCI group (n = 6, unexercised), complete transection group (n = 4, unexercised), and uninjured control group (n = 4, unexercised). Differentially expressed gene (DEG) and time-series gene investigations, functional enrichment analysis, protein-protein interaction (PPI) network construction, characteristic gene-related disease analysis, and TF-target gene interaction studies were performed. A total of 122 DEGs and 409 DEGs were respectively identified in contusion SCI versus control group and complete transection versus control group, respectively. The PPI network investigated 16 characteristic genes including corticotropin-releasing hormone (CRH), tyrosine hydroxylase (TH), and neurotensin (NTS). These genes were mainly enriched in functions involving response to ethanol, corticosterone, and estradiol. Eventually, a TF-target gene interaction network was constructed with nine TFs [including activating transcription factor 3 (ATF3)] and 10 characteristic genes. The results indicate that regulation of osteoblast differentiation and positive regulation of the BMP signaling pathway may be suppressed in the process of SCI. TH may play a pivotal role in the progression of SCI. In addition, DEGs such as CRH and NTS may be novel targets for SCI therapy.

Gal-3 is a potential biomarker for spinal cord injury and Gal-3 deficiency attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway.

Spinal cord injury (SCI) often occurs in young and middle-aged population. The present study aimed to clarify the function of Galectin-3 (Gal-3) in neuroinflammation of SCI. Sprague–Dawley (SD) rat models with SCI were established in vivo. PC12 cell model in vitro was induced by lipopolysaccharide (LPS). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gene chip were used to analyze the expression levels of genes in the signaling pathway. Histological assessment, ELISA and Western blotting were conducted to evaluate the effects of Gal-3 upon the SCI model. In the in vivo SD rat model, Gal-3 expression level was up-regulated. The inhibition of Gal-3 attenuated the neuroinflammation in SCI model. The inhibition of Gal-3 could also mitigate the neuroinflammation and reactive oxygen species (ROS) in in vitro model. ROS reduced the effect of Gal-3 on oxidative stress in in vitro model. Down-regulating the content of TXNIP decreased the effect of Gal-3 on neuroinflammation in in vitro model. Suppressing the level of NLRP3 could weaken the effect of Gal-3 on neuroinflammation in in vitro model. Our data highlight that the Gal-3 plays a vital role in regulating the severity of neuroinflammation of SCI by enhancing the activation of ROS/TXNIP/NLRP3 signaling pathway. In addition, inflammasome/IL-1β production probably acts as the therapeutic target in SCI.

Serum cystatin C is increased in acute spinal cord injury: a multicentre retrospective study

Study designA multicentre retrospective study.ObjectiveA multicentre retrospective study was performed to observe the changes in serum cystatin C (CysC) levels in patients with acute spinal cord injury (SCI).SettingFour hospitals in China.MethodsOver a 5-year study period, the CysC, creatinine (Cr), and blood urea nitrogen (BUN) levels of people who had incurred SCI in the preceding 7 days were collected and compared with those of people with limb fracture (LF) who were matched for injury time and gender. People with SCI also were grouped by injury duration, ASIA Impairment Scale (AIS) grade and the presence or absence of steroid therapy and compared each day.ResultsThree hundred and twenty-three samples from people with SCI were retrospectively collected; their mean serum CysC levels were significantly higher than those of people with LF (p < 0.001); No significant difference was observed in Cr or BUN levels between the two groups (p > 0.14). CysC levels increased on the second day, peaked on day 3, and returned to normal on day 5. The more severely injured individuals had higher CysC levels. Steroid therapy or not had no influence for CysC levels.ConclusionCysC levels are increased in patients with acute SCI, possibly as a direct result of injury. Serum CysC is a potential biomarker of SCI.

Relationships between microRNA-20a and microRNA-125b expression and apoptosis and inflammation in experimental spinal cord injury

ABSTRACTObjectives: The aim of the study was to determine the relationships between microRNA-20a and microRNA-125b expression and apoptosis and inflammation in a rat model of spinal cord injury (SCI) using microscopy, immunohistochemistry, and molecular biology.Methods: Sixty-one rats were divided into three groups: a control group that was not subjected to any operation; a sham-operated group; and an experimental group that was subjected to spinal cord compression. The experimental group was further subdivided into two subgroups: the experimental control group, which did not receive any drug treatment; and the methylprednisolone treatment group, which received 30 mg/kg methylprednisolone on day 0 followed by 10 mg/kg/day methylprednisolone from days 1–14.Results: Tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 levels increased in the experimental control group on days 1 and 3, and decreased in the experimental control group and methylprednisolone treatment group on days 7 and 14. Caspase-3 levels increased in the experimental control group on day 1, and decreased in the experimental control group and methylprednisolone treatment group on days 3, 7, and 14. MicroRNA-20a expression was upregulated in the experimental control group on days 1 and 3, and microRNA-125b expression was downregulated on days 3 and 7.Conclusions: After SCI, upregulated microRNA-20a expression and increased proinflammatory cytokines may lead to an increase in inflammation. MicroRNA-125b may be associated with caspase-3, and microRNA-125b downregulation may inhibit apoptosis. Although the results of this study suggest potential relationships between microRNA-20a and microRNA-125b expression and apoptosis and inflammation in SCI, further studies are needed to confirm microRNA-20a and microRNA-125b as biomarkers in SCI and to develop new strategies for the treatment of SCI.

Neurochemical biomarkers in spinal cord injury.

This is a narrative review of the literature on neurochemical biomarkers in spinal cord injury (SCI). The objective was to summarize the literature on neurochemical biomarkers in SCI and describe their use in facilitating clinical trials for SCI. Clinical trials in spinal cord injury (SCI) have been notoriously difficult to conduct, as exemplified by the paucity of definitive prospective randomized trials that have been completed, to date. This is related to the relatively low incidence and the complexity and heterogeneity of the human SCI condition. Given the increasing number of promising approaches that are emerging from the laboratory which are vying for clinical evaluation, novel strategies to help facilitate clinical trials are needed. A literature review was conducted, with a focus on neurochemical biomarkers that have been described in human neurotrauma. We describe advances in our understanding of neurochemical biomarkers as they pertain to human SCI. The application of biomarkers from serum and cerebrospinal fluid (CSF) has been led by efforts in the human traumatic brain injury (TBI) literature. A number of promising biomarkers have been described in human SCI whereby they may assist in stratifying injury severity and predicting outcome. Several time-specific biomarkers have been described for acute SCI and for chronic SCI. These appear promising for stratifying injury severity and potentially predicting outcome. The subsequent application within a clinical trial will help to demonstrate their utility in facilitating the study of novel approaches for SCI.

Comment: MRI provides insights into remote degeneration after cervical cord injury.

In addition to the primary damage, traumatic spinal cord injury (SCI) involves complex pathophysiologic processes at distant cord areas from the injury. The study by David et al.1 assessed the interaction between degenerative processes at and caudal to a cervical SCI lesion using diffusion tensor imaging (DTI)–derived metrics including fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity, and their relation to electrophysiologic and clinical measures of the lower extremity. DTI metrics are sensitive biomarkers of SCI between acute and chronic stages, and has the potential to provide insight into axonal integrity within and adjacent to the SCI lesion noninvasively.2

Serum and Cerebrospinal Fluid Levels of S-100β Is A Biomarker for Spinal Cord Injury; a Systematic Review and Meta-Analysis.

There is controversy regarding the value of serum or cerebrospinal fluid (CSF) levels of S100 calcium-binding protein B (S-100B) in spinal cord injury (SCI). For reaching a general conclusion, the present meta-analysis was designed aiming to evaluate the value of serum and CSF levels of S-100B protein in detecting the presence of SCI in animal studies. An extensive search was performed in Medline, Embase, Scopus and Web of science databases. Screening articles, summarizing them and entering data to checklist and quality assessment of the mentioned articles were done by 2 independent reviewers. Data were analyzed and a pooled standardized mean difference (SMD) and 95% confidence interval (95% CI) were presented. Finally, the data of 7 articles were included in the meta-analysis. Serum level of S-100B had increased as a result of SCI. During the first 6 hours after injury, the level of this protein was very high (SMD=3.8; 95% CI: 2.6 to 5.1; p<0.0001), but as time passed the serum level of the protein had decreased (SMD=0.4; 95% CI: -1.2 to 2.0; p=0.65). In addition, CSF level of the mentioned protein was very high during the initial 6 hours after injury (SMD: 5.8; 95% CI: 3.6 to 8.0), and this elevated level was still observed until 12 hours after injury (SMD: 6.5; 95% CI: 3.7 to 9.3; p<0.0001). The results of the present systematic review and meta-analysis show that measuring the level of S-100Β protein in serum and CSF has a potential value in diagnosis of SCI in animal models. This biomarker increases during the initial 6 hours following injury and remains high until 24 hours after that. However, more than 24 hours after the injury, serum level of this protein returns to the level of animals without SCI.

Biomarkers in Spinal Cord Injury: Prognostic Insights and Future Potentials.

Spinal Cord Injury (SCI) is a major challenge in Neurotrauma research. Complex pathophysiological processes take place immediately after the injury and later on as the chronic injury develops. Moreover, SCI is usually accompanied by traumatic injuries because the most common modality of injury is road traffic accidents and falls. Patients develop significant permanent neurological deficits that depend on the extent and the location of the injury itself and in time they develop further neurological and body changes that may risk their mere survival. In our review, we explored the recent updates with regards to SCI biomarkers. We observed two methods that may lead to the appearance of biomarkers for SCI. First, during the first few weeks following the injury the Blood Spinal Cord Barrier (BSCB) disruption that releases several neurologic structure components from the injured tissue. These components find their way to Cerebrospinal Fluid (CSF) and the systemic circulation. Also, as the injury develops several components of the pathological process are expressed or released such as in neuroinflammation, apoptosis, reactive oxygen species, and excitotoxicity sequences. Therefore, there is a growing interest in examining any correlations between these components and the degrees or the outcomes of the injury. Additionally, some of the candidate biomarkers are theorized to track the progressive changes of SCI which offers an insight on the patients' prognoses, potential-treatments-outcomes assessment, and monitoring the progression of the complications of chronic SCI such as Pressure Ulcers and urinary dysfunction. An extensive literature review was performed covering literature, published in English, until February 2018 using the Medline/PubMed database. Experimental and human studies were included and titles, PMID, publication year, authors, biomarkers studies, the method of validation, relationship to SCI pathophysiology, and concluded correlation were reported. Potential SCI biomarkers need further validation using clinical studies. The selection of the appropriate biomarker group should be made based on the stage of the injuries, the accompanying trauma and with regards to any surgical, or medical interference that might have been done. Additionally, we suggest testing multiple biomarkers related to the several pathological changes coinciding to offer a more precise prediction of the outcome.

Therapeutic hypothermia effectively reduces elevated extracellular ascorbate concentrations caused by acute spinal cord injury

In recent years, systemic hypothermia has taken the spotlight for its use in spinal cord injury (SCI) research fields, but detailed molecular mechanisms are still not fully understood. In this study, we use an online-electrochemical system (OECS) to in vivo continuously monitor the ascorbate of the rats’ spinal cord. We find that the basal level of ascorbate in rat spinal cord is 1.85 ± 0.88 μmol L−1 (n = 20). It increased immediately after SCI and reached 2.36 ± 0.65 μmol L−1 (164.90% ± 7.99% of the basal level) (n = 5) at 60 min after the injury. The SCI-induced extracellular ascorbate increase is obviously attenuated by therapeutic hypothermia (28 °C) after injury and ascorbate returns to 3.01 ± 0.59 μmol L−1 (100.24% ± 5.02% of the basal level) (n = 5), at 60 min after SCI. These results substantially manifest that the OECS for ascorbate detection could be employed as a platform for understanding the pathological changes during spinal cord injury. This study provides experimental evidence for the essential roles of ascorbate in SCI which could serve as a biomarker for SCI. Our findings also raise the possibility that therapeutic hypothermia can effectively exert neuroprotection in the acute phase of SCI.

Longitudinal In Vivo Diffusion Magnetic Resonance Imaging Remote from the Lesion Site in Rat Spinal Cord Injury.

Diffusion tensor imaging (DTI) has demonstrated success as a biomarker of spinal cord injury (SCI) severity as shown from numerous pre-clinical studies. However, artifacts from stabilization hardware at the lesion have precluded its use for longitudinal assessments. Previous research has documented ex vivo diffusion changes in the spinal cord both caudal and cranial to the injury epicenter. The aim of this study was to use a rat contusion model of SCI to evaluate the utility of in vivo cervical DTI after a thoracic injury. Forty Sprague-Dawley rats underwent a thoracic contusion (T8) of mild, moderate, severe, or sham severity. Magnetic resonance imaging (MRI) of the cervical cord was performed at 2, 30, and 90 days post-injury, and locomotor performance was assessed weekly using the Basso, Bresnahan, and Beattie (BBB) scoring scale. The relationships between BBB scores and MRI were assessed using region of interest analysis and voxel-wise linear regression of DTI, and free water elimination (FWE) modeling to reduce partial volume effects. At 90 days, axial diffusivity (ADFWE), mean diffusivity (MDFWE), and free water fraction (FWFFWE) using the FWE model were found to be significantly correlated with BBB score. FWE was found to be more predictive of injury severity than conventional DTI, specifically at later time-points. This study validated the use of FWE technique in spinal cord and demonstrated its sensitivity to injury remotely.

Hyperphosphorylated Tau as a Novel Biomarker for Traumatic Axonal Injury in the Spinal Cord.

Current biomarker research in spinal cord injury (SCI) and traumatic brain injury has focused on a number of structural protein candidates, including the microtubule-associated protein tau. Evidence from models of traumatic brain injury has demonstrated that hyperphosphorylation of tau (p-tau) occurs in injured axons and demonstrates its utility as a biomarker for brain injury; however, the potential of p-tau as a biomarker for SCI is not yet known. Therefore, the present study determined whether tau is hyperphosphorylated in injured spinal cord axons, and then examined cerebrospinal fluid (CSF) and serum concentrations of p-tau and total-tau protein after a clinically relevant severe impact-compression SCI in rats. We found that severe SCI at T8 showed the presence of p-tau in damaged axons with a similar time course and distribution pattern to β-APP, a biomarker of axonal injury. The presence of p-tau and β-APP positive axons extended no farther than 5000 μm rostral and caudal to the injury epicenter, and was at its maximum at one day post-SCI. CSF levels of p-tau and total-tau significantly increased at one day post-SCI; however, only serum p-tau levels were significantly elevated in rats with SCI compared with naïve rats. These results suggest that CSF and serum p-tau may be a useful biomarker for severe traumatic SCI.

Bioinformatic Analysis of Potential Biomarkers for Spinal Cord-injured Patients with Intractable Neuropathic Pain.

Background:Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting individuals’ quality of life. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and microRNAs (miRNAs) related to neuropathic pain by the bioinformatics method.Methods:Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from individuals with or without neuropathic pain after SCI were collected. Twelve samples from individuals with neuropathic pain and 13 samples from individuals without pain as controls were included in the downloaded microarray. Differentially expressed genes (DEGs) between the neuropathic pain group and the control group were detected using the GEO2R online tool. Functional enrichment analysis of DEGs was performed using the DAVID database. Protein-protein interaction network was constructed from the STRING database. MiRNAs targeting these DEGs were obtained from the miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software.Results:In total, 1134 DEGs were identified between individuals with or without neuropathic pain (case and control), and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be potential biomarkers for SCI patients.Conclusion:Protein modification and regulation of the biological process of the central nervous system may be a risk factor in SCI. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for the prevention and treatment of neuropathic pain after SCI.

Biomarkers in Spinal Cord Injury: from Prognosis to Treatment.

Spinal cord injury (SCI) is considered an incurable condition, having a heterogenous recovery and uncertain prognosis. Therefore, a reliable prediction of the improvement in the acute phase could benefit patients. Physicians are unanimous in insisting that at the initial damage of the spinal cord (SC), the patient should be carefully evaluated in order to help selecting an appropriate neuroprotective treatment. However, currently, neurologic impairment after SCI is measured and classified by functional examination. The identification of prognostic biomarkers of SCI would help to designate SC injured patients and correlate to diagnosis and correct treatment. Some proteins have already been identified as good potential biomarkers of central nervous system injury, both in cerebrospinal fluid (CSF) and blood serum. However, the problem for using them as biomarkers is the way they should be collected, as acquiring CSF through a lumbar puncture is significantly invasive. Remarkably, microRNAs (miRNAs) have emerged as interesting biomarker candidates because of their stability in biological fluids and their tissue specificity. Several miRNAs have been identified to have their expressions altered in SCI in many animal models, making them promising candidates as biomarkers after SCI. Moreover, there are yet no effective therapies for SCI. It is already known that altered lysophospholipids (LPs) signaling are involved in the biology of disorders, such as inflammation. Reports have demonstrated that LPs when locally distributed can regulate SCI repair and key secondary injury processes such as apoptosis and inflammation, and so could become in the future new therapeutic approaches for treating SCI.

Optimizing Filter-Probe Diffusion Weighting in the Rat Spinal Cord for Human Translation.

Diffusion tensor imaging (DTI) is a promising biomarker of spinal cord injury (SCI). In the acute aftermath, DTI in SCI animal models consistently demonstrates high sensitivity and prognostic performance, yet translation of DTI to acute human SCI has been limited. In addition to technical challenges, interpretation of the resulting metrics is ambiguous, with contributions in the acute setting from both axonal injury and edema. Novel diffusion MRI acquisition strategies such as double diffusion encoding (DDE) have recently enabled detection of features not available with DTI or similar methods. In this work, we perform a systematic optimization of DDE using simulations and an in vivo rat model of SCI and subsequently implement the protocol to the healthy human spinal cord. First, two complementary DDE approaches were evaluated using an orientationally invariant or a filter-probe diffusion encoding approach. While the two methods were similar in their ability to detect acute SCI, the filter-probe DDE approach had greater predictive power for functional outcomes. Next, the filter-probe DDE was compared to an analogous single diffusion encoding (SDE) approach, with the results indicating that in the spinal cord, SDE provides similar contrast with improved signal to noise. In the SCI rat model, the filter-probe SDE scheme was coupled with a reduced field of view (rFOV) excitation, and the results demonstrate high quality maps of the spinal cord without contamination from edema and cerebrospinal fluid, thereby providing high sensitivity to injury severity. The optimized protocol was demonstrated in the healthy human spinal cord using the commercially-available diffusion MRI sequence with modifications only to the diffusion encoding directions. Maps of axial diffusivity devoid of CSF partial volume effects were obtained in a clinically feasible imaging time with a straightforward analysis and variability comparable to axial diffusivity derived from DTI. Overall, the results and optimizations describe a protocol that mitigates several difficulties with DTI of the spinal cord. Detection of acute axonal damage in the injured or diseased spinal cord will benefit the optimized filter-probe diffusion MRI protocol outlined here.

The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ¹H NMR spectroscopy

To establish the rat model of acute spinal cord injury, followed by aprimary study on this model with ¹H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat. Twenty eight-week-old adult male SD rats of clean grade, with body weight of (200±10) g, were divided into sham operation group and model group in accordance with the law of random numbers, and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord, and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen's method. According to BBB score to observate the motor function of rats on the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day, and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by ¹H NMR spectroscopy. The hindlimb motion of rats did not obviously change in sham operation group, there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities, there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group, while in model group, the spinal cord structure was mussy, and the neurons were decreased, with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein (VLDL), low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA), glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had significant changes(P<0.05). There are significant differences in metabolic profile from serum and spinal cord sample between model group and sham operation group, it conduces to explain the changes of small molecular substances in serum and spinal cord tissue after spinal cord injury, this provides the research basis for targeted research on the role of metabolic markers in patients with acute spinal cord injury.

The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood.

Review study. The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trials. The objective of this review is to evaluate the current state-of-play in this developing field. Studies from multiple countries were included. We have completed a comprehensive review of studies that have investigated prognostic biomarkers in either the blood or cerebrospinal fluid (CSF) of animals and humans following SCI. Targeted and unbiased approaches have identified several prognostic biomarkers in CSF and blood. These proteins associate with cellular damage following SCI and include components from neurons, oligodendrocytes and reactive astrocytes, that is, neurofilament proteins, glial fibrillary acidic protein, Tau and S100 calcium-binding protein β. Unbiased approaches have also identified microRNAs that are specific to SCI, as well as other cell damage-associated proteins. The discovery and validation of stable, specific, sensitive and reproducible biomarkers of SCI is a rapidly expanding field of research. So far, few studies have utilised unbiased approaches aimed at the discovery of biomarkers within the CSF or blood in this field; however, some targeted approaches have been successfully used. Several studies using various animal models and some with small human patient cohorts have begun to pinpoint biomarkers in the CSF and blood with putative prognostic value. An increased sample size will be required to validate these biomarkers in the heterogeneous clinical setting.

Biomarkers in spinal cord compression Ethics and perspectives

Abstract The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H) in serum or in cerebro-spinal fluid (CSF) is a specific lesional biomarker for spinal cord injury. The lesional biomarkers and the reaction biomarkers are both presented after several hours post-injury. The specific predictive patterns of lesional biomarkers could be used to aid clinicians with making a diagnosis and establishing a prognosis, and evaluating therapeutic interventions. Diagnosis, prognosis, and treatment guidance based on biomarker used as a predictive indicator can determine ethical difficulties by differentiated therapies in patients with spinal cord compression. At this point based on studies until today we cannot take a decision based on biomarker limiting the treatment of neurological recovery in patients with complete spinal cord injury because we do not know the complexity of the biological response to spinal cord compression.

18F-FDG-PET imaging of rat spinal cord demonstrates altered glucose uptake acutely after contusion injury

Spinal cord injury (SCI) results in an acute reduction in neuronal and glial cell viability, disruption in axonal tract integrity, and prolonged increases in glial activity and inflammation, all of which can influence regional metabolism and glucose utilization. To date, the understanding of glucose uptake and utilization in the injured spinal cord is limited. Positron emission tomography (PET)-based measurements of glucose uptake may therefore serve as a novel biomarker for SCI. This study aimed to determine the acute and sub-acute glucose uptake pattern after SCI to determine its potential as a novel non-invasive tool for injury assessment and to begin to understand the glucose uptake pattern following acute SCI. Briefly, adult male Sprague-Dawley rats were subjected to moderate contusion SCI, confirmed by locomotor function and histology. PET imaging with [18F] Fluorodeoxyglucose (FDG) was performed prior to injury and at 6 and 24h and 15days post-injury (dpi). FDG-PET imaging revealed significantly depressed glucose uptake at 6h post-injury at the lesion epicenter that returned to sham/naïve levels at 24h and 15 dpi after moderate injury. FDG uptake at 15 dpi was likely influenced by a combination of elevated glial presence and reduced neuronal viability. These results show that moderate SCI results in acute depression in glucose uptake followed by an increase in glucose uptake that may be related to neuroinflammation. This acute and sub-acute uptake, which is dependent on cellular responses, may represent a therapeutic target.

New Surgical Attitude in Complete Acute Traumatic Spinal Cord Injury

IntroductionStudies have shown the values pattern of the phosphorylated form of the high-molecular-weight neurofilament subunit (pNF-H) in CSF is a predictive biomarker for acute traumatic spinal cord injury (SCI). Materials and MethodsA previous study of pNF-H in CSF of patients with SCI showed it is a specific biomarker for SCI, it can distinguish the severity of SCI and it is a predictive biomarker because of its values pattern can show the reducing or stopping of the secondary lesion and a favorable result. At 22 subjects with acute traumatic SCI we correlated the pNF-H concentration in CSF with the MRI, with the diffusion tensor tractography on the SCI site and with the clinical evolution. All patients underwent surgery during the first 24 hours (decompression, stabilization). In two cases with unfavorable pattern of pNF-H after 4 and 7 days, MRI identified the SCI site with an extensive spinal cord edema and a necrotic cavity. A second microneurosurgery was done: opening the dura 5 levels, duraplasty and opening the spinal cord in the midline and debridement of the necrotic tissue. ResultsComplete SCI cases had a specific pattern of values of pNF-H correlated with the MRI and the clinical evolution. A second microneurosurgery solved the cord edema and the spinal cord laceration. One case has improved progressively after 6 months and the other case - no neurological improvement after one year of rehabilitation. ConclusionsPatients must undergo surgery during the first 24 hours: a large decompression on 5 – 7 levels with duraplasty and stabilization. After these we can use the predictive unfavorable pattern of pNF-H correlated with MRI and a second microneurosurgery in SCI site must be done: opening the spinal cord in the midline and microsurgical debridement of the necrotic tissue. This surgical attitude can create favorable conditions for functional recovery of the remaining spinal cord.

Increased S-nitrosothiols are associated with spinal cord injury in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disorder associated with inflammation, demyelination and axonal damage. In search of potential biomarkers of spinal cord lesions in MS related to nitric oxide metabolites, we measured total nitrite and nitrate levels, and protein-bound nitrotyrosine and S-nitrosothiol concentrations in the serum of MS patients at different stages of the disease. Sixty-eight patients and 36 healthy volunteers were included in the study. Total nitrite and nitrate levels were augmented in relapsing-remitting MS, while increased S-nitrosothiol concentrations were found both in relapsing-remitting and secondary-progressive MS. Further analysis demonstrated that S-nitrosothiol levels were selectively increased in patients with spinal cord injury. The data suggest that high S-nitrosothiol concentration may be a potential serum biomarker for spinal cord injury in MS.