Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury

Abstract

Suffering an acute spinal cord injury (SCI) can result in catastrophic physical and emotional loss. Efforts to translate novel therapies in acute clinical trials are impeded by the SCI community’s singular dependence upon functional outcome measures. Therefore, a compelling rationale exists to establish neurochemical biomarkers for the objective classification of injury severity. In this study, CSF and serum samples were obtained at 3 time points (~24, 48, and 72 hours post-injury) from 30 acute SCI patients (10 AIS A, 12 AIS B, and 8 AIS C). A differential chemical isotope labeling liquid chromatography mass spectrometry (CIL LC-MS) with a universal metabolome standard (UMS) was applied to the metabolomic profiling of these samples. This method provided enhanced detection of the amine- and phenol-containing submetabolome. Metabolic pathway analysis revealed dysregulations in arginine-proline metabolism following SCI. Six CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC > 0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients. Using the UMS strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome.

The Impact of GFP Reporter Gene Transduction and Expression on Metabolomics of Placental Mesenchymal Stem Cells Determined by UHPLC-Q/TOF-MS

“…By searching the 1151 peak pairs against the dansyl standard library, which consists of 273 labeled standards [ 17 ], using a mass tolerance of 10 ppm and a retention time (RT) tolerance of 30 s, 89 metabolites were positively identified based on mass and RT matches (see online Supplementary Table S1A for the list). Using MyCompoundID [ 18 ] MS search based on the accurate mass of the peak pairs with a mass tolerance of 10 ppm, 281 metabolites were putatively identified using the HMDB library (see online Supplementary Table S1B), and 458 metabolites were putatively identified using the predicted human metabolite library (EML) with one reaction (see online Supplementary Table S1C).…”

Gambogic acid inhibits spinal cord injury and inflammation through suppressing the p38 and Akt signaling pathways

“…An SCI model was induced as previously described (14). In the SCI model and GA groups, rats were anesthetized with pentobarbital sodium (35 mg/kg, intraperitoneally; Sigma-Aldrich; Merck KGaA, Darmstadt, Germany), and laminectomy was performed at the T9-T11 level in every rat, which exposed the underlying cord.…”

Unbiased Recursive Partitioning to Stratify Patients with Acute Traumatic Spinal Cord Injuries: External Validity in an Observational Cohort Study

“…Improved prediction may be achieved by combining such clinical features with objective magnetic resonance imaging biomarkers and/or neurochemical biomarkers from cerebrospinal fluid or blood. 7,26,27 While the use of early motor scores to predict later recovery is conceptually appealing for clinicians, our application of this approach to an independent dataset of complete SCI subjects did not reveal the ability to clearly discern different motor score outcomes. Further study is therefore warranted to establish the parameters by which early motor scores may be used to substratify patients who are enrolled into clinical trials of novel therapeutics.…”