Cerebrospinal Fluid Metabolomics After Natural Product Treatment in an Experimental Model of Cerebral Ischemia

OMICS. 2016 Nov;20(11):670-680. doi: 10.1089/omi.2016.0112. Epub 2016 Oct 12.

Abstract

Cerebrospinal fluid (CSF) is an important biofluid for diagnosis of and research on neurological diseases. However, in-depth metabolomic profiling of CSF remains an analytical challenge due to the small volume of samples, particularly in small animal models. In this work, we report the application of a high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) workflow for CSF metabolomics in Gastrodia elata and Uncaria rhynchophylla water extract (GUW)-treated experimental cerebral ischemia model of rat. The GUW is a commonly used Traditional Chinese Medicine (TCM) for hypertension and brain disease. This study investigated the amine- and phenol-containing biomarkers in the CSF metabolome. After GUW treatment for 7 days, the neurological deficit score was significantly improved with infarct volume reduction, while the integrity of brain histological structure was preserved. Over 1957 metabolites were quantified in CSF by dansylation LC-MS. The analysis of this comprehensive list of metabolites suggests that metabolites associated with oxidative stress, inflammatory response, and excitotoxicity change during GUW-induced alleviation of ischemic injury. This work is significant in that (1) it shows CIL LC-MS can be used for in-depth profiling of the CSF metabolome in experimental ischemic stroke and (2) identifies several potential molecular targets (that might mediate the central nervous system) and associate with pharmacodynamic effects of some frequently used TCMs.

Keywords: LC-MS; cerebrospinal fluid; chemical isotope labeling; metabolomics; middle cerebral artery occlusion; natural product extract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / analysis
  • Animals
  • Biological Products / therapeutic use*
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Brain Ischemia / cerebrospinal fluid*
  • Brain Ischemia / pathology
  • Brain Ischemia / therapy*
  • Cerebrospinal Fluid Proteins / analysis
  • Cerebrospinal Fluid Proteins / metabolism*
  • Chromatography, Liquid / methods
  • Disease Models, Animal
  • Drugs, Chinese Herbal / therapeutic use
  • Gastrodia
  • Male
  • Mass Spectrometry / methods
  • Medicine, Chinese Traditional
  • Metabolomics / methods*
  • Phenols / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Stroke / cerebrospinal fluid*
  • Stroke / pathology
  • Stroke / therapy*
  • Uncaria

Substances

  • Amines
  • Biological Products
  • Biomarkers
  • Cerebrospinal Fluid Proteins
  • Drugs, Chinese Herbal
  • Phenols

Grant support