Bioinformatics analysis of ferroptosis in spinal cord injury.

Ferroptosis plays a key role in aggravating the progression of spinal cord injury (SCI), but the specific mechanism remains unknown. In this study, we constructed a rat model of T10 SCI using a modified Allen method. We identified 48, 44, and 27 ferroptosis genes that were differentially expressed at 1, 3, and 7 days after SCI induction. Compared with the sham group and other SCI subgroups, the subgroup at 1 day after SCI showed increased expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 and the oxidative stress marker malondialdehyde in the injured spinal cord while glutathione in the injured spinal cord was lower. These findings with our bioinformatics results suggested that 1 day after SCI was the important period of ferroptosis progression. Bioinformatics analysis identified the following top ten hub ferroptosis genes in the subgroup at 1 day after SCI: STAT3, JUN, TLR4, ATF3, HMOX1, MAPK1, MAPK9, PTGS2, VEGFA, and RELA. Real-time polymerase chain reaction on rat spinal cord tissue confirmed that STAT3, JUN, TLR4, ATF3, HMOX1, PTGS2, and RELA mRNA levels were up-regulated and VEGFA, MAPK1 and MAPK9 mRNA levels were down-regulated. Ten potential compounds were predicted using the DSigDB database as potential drugs or molecules targeting ferroptosis to repair SCI. We also constructed a ferroptosis-related mRNA-miRNA-lncRNA network in SCI that included 66 lncRNAs, 10 miRNAs, and 12 genes. Our results help further the understanding of the mechanism underlying ferroptosis in SCI.

Identification of key genes involved in recovery from spinal cord injury in adult zebrafish.

Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord injury. The subacute phase after spinal cord injury is critical to the recovery of neurological function, which involves tissue bridging and axon regeneration. In this study, we found that zebrafish spontaneously recovered 44% of their swimming ability within the subacute phase (2 weeks) after spinal cord injury. During this period, we identified 7762 differentially expressed genes in spinal cord tissue: 2950 were up-regulated and 4812 were down-regulated. These differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain, axon regeneration, and cell-component morphogenesis. The genes were also mostly involved in the regulation of metabolic pathways, the cell cycle, and gene-regulation pathways. We verified the gene expression of two differentially expressed genes, clasp2 up-regulation and h1m down-regulation, in zebrafish spinal cord tissue in vitro. Pathway enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein, which is responsible for axon extension regulated by microtubules. Down-regulated h1m controls endogenous stem cell differentiation after spinal cord injury. This study provides new candidate genes, clasp2 and h1m, as potential therapeutic intervention targets for spinal cord injury repair by neuroregeneration. All experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical & Pharmaceutical Sciences (approval No. IMPS-EAEP-Q-2019-02) on September 24, 2019.

Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4.

Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury. High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma. In this study, we established an oligodendrocyte (OLN-93 cell line) model of ferroptosis induced by RSL-3, an inhibitor of glutathione peroxidase 4 (GPX4). RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde. RSL-3 also inhibited the main anti-ferroptosis pathway, i.e., SLC7A11/glutathione/glutathione peroxidase 4 (xCT/GSH/GPX4), and downregulated acyl-coenzyme A synthetase long chain family member 4. Furthermore, we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis. Liproxstatin-1 was more potent than edaravone or deferoxamine. Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation, but also restored the expression of GSH, GPX4 and ferroptosis suppressor protein 1. These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes, and that liproxstatin-1 is a potent inhibitor of ferroptosis. Therefore, liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.

Neuroprotective effect of deferoxamine on erastininduced ferroptosis in primary cortical neurons.

The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury. However, it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death. By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin, it was found that these cell types respond differentially to the duration and concentration of erastin treatment. Therefore, we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos. After treatment with 50 µM erastin for 48 hours, reactive oxygen species levels increased, and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased. Pretreatment with deferoxamine for 12 hours inhibited these changes, reduced cell death, and ameliorated cellular morphology. Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis. Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin, confirming the specificity of the in vitro ferroptosis model. This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences, China (approval No. DWLL-20180913) on September 13, 2018.

MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronal-like cells by Schwann cell-conditioned medium.

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesenchymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis identified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathways were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311).

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis.

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows: (1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group. (2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group. (3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury. (4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group. (5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2 (ACSF2) and iron-responsive element-binding protein 2 (IREB2) were up-regulated in the Deferoxamine group. (6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.

Abnormal DNA Methylation in Thoracic Spinal Cord Tissue Following Transection Injury.

BACKGROUND Spinal cord injury (SCI) is a serious disease with high disability and mortality rates, with no effective therapeutic strategies available. In SCI, abnormal DNA methylation is considered to be associated with axonal regeneration and cell proliferation. However, the roles of key genes in potential molecular mechanisms of SCI are not clear. MATERIAL AND METHODS Subacute spinal cord injury models were established in Wistar rats. Histological observations and motor function assessments were performed separately. Whole-genome bisulfite sequencing (WGBS) was used to detect the methylation of genes. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database. Protein-protein interaction (PPI) networks were analyzed by Cytoscape software. RESULTS After SCI, many cavities, areas of necrotic tissue, and many inflammatory cells were observed, and motor function scores were low. After the whole-genome bisulfite sequencing, approximately 96 DMGs were screened, of which 50 were hypermethylated genes and 46 were hypomethylated genes. KEGG pathway analysis highlighted the Axon Guidance pathway, Endocytosis pathway, T cell receptor signaling pathway, and Hippo signaling pathway. Expression patterns of hypermethylated genes and hypomethylated genes detected by qRT-PCR were the opposite of WGBS data, and the difference was significant. CONCLUSIONS Abnormal methylated genes and key signaling pathways involved in spinal cord injury were identified through histological observation, behavioral assessment, and bioinformatics analysis. This research can serve as a source of additional information to expand understanding of spinal cord-induced epigenetic changes.

iTRAQ-based proteomics profiling of Schwann cells before and after peripheral nerve injury.

OBJECTIVES: Schwann cells (SCs) have a wide range of applications as seed cells in the treatment of nerve injury during transplantation. However, there has been no report yet on kinds of proteomics changes that occur in Schwann cells before and after peripheral nerve injury. MATERIALS AND METHODS: Activated Schwann cells (ASCs) and normal Schwann cells (NSCs) were obtained from adult Wistar rat sciatic nerves. After immunofluorescence identification, we identified differentially expressed proteins in the ASCs and NSCs using isobaric tags for relative and absolute quantitation (iTRAQ) combined with high-resolution Orbitrap liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In addition, all the differentially expressed proteins were analyzed by Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Finally, several differentially expressed proteins were selected for Western blot verification. RESULTS: A total of 122 differentially expressed proteins in ASCs and NSCs were screened. GO analysis suggested that these different proteins are likely to accumulate in the cytoplasm and are associated with single-multicellular organism processes. The KEGG pathway analysis suggested that proteins related to purine metabolism were significantly enriched. The expression of Transmembrane glycoprotein NMB (GPNMB), Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3), and other proteins were consistent with the proteomics data obtained by Western blot analysis. CONCLUSION: GPNMB, ENPP3, GFPT2, and other proteins may play an important role in the repair of peripheral nerve injury. This study may provide new insights into changes in SCs after peripheral nerve injury.

Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury.

AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat. Hematoxylin and eosin staining (H&E staining) and Luxol fast blue (LFB) staining were used to observe the histological lesions. Apoptosis was examined by TUNEL staining, Annexin V-FITC/PI, caspase-3, and Bcl-2. Cytokines and neurotrophins were tested by Western blot. Locomotion recovery assessed by hindlimb BBB score and the inclined plane test. RESULTS: Nafamostat mesilate treatment significantly improved locomotion recovery as assessed by hindlimb BBB scores and the inclined plane test. H&E staining and LFB staining showed a significant increase in spared tissue in both gray matter and white matter. NM decreased the expression of the proinflammatory cytokines TNF-α and IL-6. In addition, apoptosis was also significantly decreased, as shown by TUNEL staining and Annexin V-FITC/PI and by Western blotting for caspase-3 and Bcl-2 expression. Due to the mechanism of action of NM as a serine protease inhibitor, the drug decreased thrombin expression in the damaged spinal cord. Furthermore, NM increased the expression of neurotrophins (NT-3, BDNF, and NGF). CONCLUSIONS: Upon NM treatment, the functional and histological outcomes were improved, and microenvironment upon SCI was modulated. As a clinically approved drug, NM holds promise for clinical use after spinal cord injury.

Differential expression of miRNAs in Osborne's ligament of cubital tunnel syndrome.

Cubital tunnel syndrome (CuTS) is the second most common peripheral nerve compression disease, however, the pathogenesis and pathology of CuTS remain to be fully elucidated. The aim of the present study was to compare the expression pattern of microRNAs (miRNAs) in pachyntic Osborne's ligament with that in control tendinous tissue, and select meaningful miRNAs for further investigation of the clinical pathological mechanism underlying CuTS. A microarray assay was performed to examine the expression profiles of miRNAs in the Osborne's ligament and control tendinous tissues. An online bioinformatics algorithms tool (miRWalk) was used to predict putative target genes for the deregulated miRNAs, and functional annotation was performed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the results of microarray were partially validated using reverse transcription­quantitative polymerase chain reaction analysis. The expression of total of 60 miRNAs were found to be significantly different between the pachyntic Osborne's ligament and control tendinous tissues. MiRWalk2.0 predicted 1,804 target genes for these miRNAs, and the GO functional analysis of the predicted genes suggested cellular mechanisms, including metabolic process, regulation of cell growth, cell cycle processes, cell division regulation, cellular metabolic process and signal transmission, were involved. Furthermore, KEGG pathway analysis revealed important pathways, including adherent junction, focal adhesion, lysine degradation, cell adhesion molecules and mitogen­activated protein kinase. Compared with the heathy tissue, Osborne's ligament tissue from patients with CuTS showed a markedly different miRNA expression profile, which suggested that miRNAs may be involved in the pathogenesis of CuTS.

Comparison of DNA Methylation in Schwann Cells before and after Peripheral Nerve Injury in Rats.

This study aims to find the difference of genomewide DNA methylation in Schwann cells (SCs) before and after peripheral nerve system (PNS) injury by Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq) and seek meaningful differentially methylated genes related to repairment of injured PNS. SCs harvested from sciatic nerve were named as activated Schwann cells (ASCs), and the ones harvested from brachial plexus were named as normal Schwann cells (NSCs). Genomic DNA of ASCs and NSCs were isolated and MeDIP-Seq was conducted. Differentially methylated genes and regions were discovered and analyzed by bioinformatic methods. MeDIP-Seq analysis showed methylation differences were identified between ASCs and NSCs. The distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in distal intergenic regions. GO and KEGG analysis of these methylated genes were also conducted. The expression patterns of hypermethylated genes (Dgcr8, Zeb2, Dixdc1, Sox2, and Shh) and hypomethylated genes (Gpr126, Birc2) detected by qRT-PCR were opposite to the MeDIP analysis data with significance (p < 0.05), which proved MeDIP analysis data were real and believable. Our data serve as a basis for understanding the injury-induced epigenetic changes in SCs and the foundation for further studies on repair of PNS injury.

Efficacy and safety of tension band wiring versus plate fixation in olecranon fractures: a systematic review and meta-analysis.

BACKGROUND: Olecranon fracture (OF) is a common upper limb fracture, and the most commonly used techniques are still tension band wiring (TBW) and plate fixation (PF). The aim of the current study is to discuss whether TBW or PF technique of internal fixation is better in the treatment of OFs, using the method of meta-analysis. METHODS: The eligible studies were acquired from PubMed, CNKI, Embase, Cochrane Library, and other sources. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Thirteen studies including 1 RCT and 12 observational studies were assessed. Our meta-analysis results showed that both in RCT and observational studies, there were no significant differences between the two groups in disabilities of the arm, shoulder and hand (DASH) (SMD = 0.07, 95% CI = -0.32 to 0.46, p = 0.73), improvement rate (OR = 0.76, 95% CI = 0.48-1.22, p = 0.26), range of motion (ROM), operation time (SMD = -0.51, 95% CI = -1.17 to 0.14, p = 0.12) and blood loss (SMD = -0.97, 95% CI = -2.06 to 0.11, p = 0.08). The overall estimate of complications indicated that the pooled OR was 2.61 (95% CI = 1.65-4.14, p < 0.0001), suggesting that the difference was statistically significant. We also compared the outcomes of patients with mayo type IIA OFs treated by TBW and PF in DASH and ROM and found no differences. CONCLUSIONS: Both TBW and PF interventions had treatment benefit in OFs. The current study reveals that there are no significant differences in DASH, improvement rate, ROM, operation time, and blood loss between TBW and PF for OFs. Due to the less complications, we recommend the PF approach as the optical choice for OFs. More high-quality studies are required to further confirm our results.

Open versus endoscopic in situ decompression in cubital tunnel syndrome: A systematic review and meta-analysis.

OBJECTIVE: We conducted this systematic review and meta-analysis to compare the clinical efficacy and safety between open and endoscopic in situ decompression surgery methods for cubital tunnel syndrome (CuTS). METHODS: PubMed, Medline, Embase, Cochrane Library and CNKI were searched for eligible studies. The data were extracted by two of the coauthors (WL, BYF) independently and were analyzed using RevMan statistical software, version 5.1. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and the Newcastle-Ottawa Scale were used to assess the risk of bias. RESULTS: Seven studies were included for systematic review, and six studies were included for meta-analysis. The CuTS patients received open in situ decompression (OISD) or endoscopic in situ decompression (EISD). A pooled analysis of postoperative Bishop score showed that the difference was not statistically significant between the EISD group and the OISD group (RR = 0.99, 95% CI = 0.88-1.12, P = 0.88). The overall estimate of postoperative satisfaction between the EISD group and the OISD group was not found to be significant (RR = 0.98, 95% CI = 0.89-1.08, P = 0.70). The overall estimate of complications (RR = 0.88, 95% CI = 0.24-3.29, P = 0.85) suggested that the difference was not statistically significant. CONCLUSIONS: EISD and OISD for treating CuTS have equivalent efficacy for postoperative clinical improvement, whereas the incidences of complications of endoscopic surgical procedure were also same as those with the open surgical procedure. In situ decompression (especially EISD, with minor intraoperative trauma) could be treated as a valuable alternative to treat CuTS.

Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal tunnel syndrome: A systematic review and meta-analysis.

BACKGROUND: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disease. Either surgical or conservative intervention for CTS patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical efficacy, safety, and cost of surgical versus nonsurgical intervention. METHODS: The eligible studies were acquired from PubMed, Medline, Embase, Web of Science, Google, and Cochrane Library. The data were extracted by 2 of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Thirteen studies including 9 randomized controlled trials (RCTs) and 4 observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The difference of clinical efficacy was statistically significant between surgical and nonsurgical intervention, and nonsurgical treatment was more effective (OR = 2.35, 95%CI = 1.18-4.67, P = 0.01). Meanwhile, different results were discovered by subgroup analysis. The pooled results of function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care at different follow-up times showed that the differences were not statistically significant between the 2 interventions. The difference of complications and side-effects was statistically significant and conservative treatment achieved better result than surgery (OR = 2.03, 95%CI = 1.28-3.22, P = 0.003). Sensitivity analysis proved the stability of the pooled results. CONCLUSION: Both surgical and conservative interventions had benefits in CTS. Nonsurgical treatment was more effective and safety than surgical treatment, but there were no significant differences in function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care. Nonsurgical treatment is recommended as the optical choice for CTS. If conservative treatment fails, surgical release can be taken.

Does local lavage influence functional recovery during lumber discectomy of disc herniation?: One year's systematic follow-up of 410 patients.

Lumbar disc herniation (LDH) is a common disease and lumbar discectomy is the most common surgical procedure carried out for patients with low back pain and leg symptoms. Although most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the effect of local intervertebral lavage during microdiscectomy.In this retrospective study, 410 patients were operated on by microdiscectomy for LDH during 2011 to 2014. Retrospectively, 213 of them (group A) accepted local intervertebral irrigation with saline water before wound closure and 197 patients (group B) only had their operative field irrigated with saline water. Systematic records of visual analog scores (VAS), Oswestry disability Index (ODI) questionnaire scale scores, use of analgesia, and hospital length of stay were done after hospitalization.The majority (80.49%) of the cases were diagnosed with lumber herniation at the levels of L4/5 and L5/S1. Fifty-one patients had herniations at 2 levels. There were significant decreases of VAS scores and ODI in both groups between preoperation and postoperation of different time points. VAS scores decreased more in group A than group B at early stage of postoperation follow-up. However, there were no statistically significant differences between 2 groups in using analgesia, VAS and ODI up to 1 month of follow-up.Microdiscectomy for LDH offers a marked improvement in back and radicular pain. Local irrigation of herniated lumber disc area could relief dick herniation-derived low back pain and leg radicular pain at early stage of post-operation. However, the pain relief of this intervention was not noticeable for a long period.

Proteomic and bioinformatic analyses of spinal cord injury­induced skeletal muscle atrophy in rats.

Spinal cord injury (SCI) may result in skeletal muscle atrophy. Identifying diagnostic biomarkers and effective targets for treatment is an important challenge in clinical work. The aim of the present study is to elucidate potential biomarkers and therapeutic targets for SCI­induced muscle atrophy (SIMA) using proteomic and bioinformatic analyses. The protein samples from rat soleus muscle were collected at different time points following SCI injury and separated by two­dimensional gel electrophoresis and compared with the sham group. The identities of these protein spots were analyzed by mass spectrometry (MS). MS demonstrated that 20 proteins associated with muscle atrophy were differentially expressed. Bioinformatic analyses indicated that SIMA changed the expression of proteins associated with cellular, developmental, immune system and metabolic processes, biological adhesion and localization. The results of the present study may be beneficial in understanding the molecular mechanisms of SIMA and elucidating potential biomarkers and targets for the treatment of muscle atrophy.