Establishment of quantitative severity evaluation model for spinal cord injury by metabolomic fingerprinting

PLoS One. 2014 Apr 11;9(4):e93736. doi: 10.1371/journal.pone.0093736. eCollection 2014.

Abstract

Spinal cord injury (SCI) is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR) screening, we identified 15 metabolites that made up an "Eigen-metabolome" capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD-NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Magnetic Resonance Imaging
  • Male
  • Metabolome / physiology*
  • Metabolomics / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / diagnosis*
  • Spinal Cord Injuries / metabolism*

Grants and funding

This work was supported by grants from the Sichuan Department of Science and Technology (No. 2011SZ0139, 2011SZ0336, 2012SZ0181 and SZ20120209), the Bureau of Science and Technology of Chengdu (No. 12PPYB181SF-002 and 11PPYB099SF-289), and grants from the Sichuan Department of Health (No. 090442, No. 100552, and No. 100553). Dr. Jin Peng is supported by China Scholarship Council (No: 201206245103). The funders did not contribute to the study design, data collection and analysis, decision to publish, or manuscript preparation.