NMR and Pattern Recognition Can Distinguish Neuroinflammation and Peripheral Inflammation

Abstract

Multiple Sclerosis (MScl) is a neurodegenerative disease of the CNS, associated with chronic neuroinflammation. Cerebrospinal fluid (CSF), being in closest interaction with CNS, was used to profile neuroinflammation to discover disease-specific markers. We used the commonly accepted animal model for the neuroinflammatory aspect of MScl: the experimental autoimmune/allergic encephalomyelitis (EAE). A combination of advanced (1)H NMR spectroscopy and pattern recognition methods was used to establish the metabolic profile of CSF of EAE-affected rats (representing neuroinflammation) and of two control groups (healthy and peripherally inflamed) to detect specific markers for early neuroinflammation. We found that the CSF metabolic profile for neuroinflammation is distinct from healthy and peripheral inflammation and characterized by changes in concentrations of metabolites such as creatine, arginine, and lysine. Using these disease-specific markers, we were able to detect early stage neuroinflammation, with high accuracy in a second independent set of animals. This confirms the predictive value of these markers. These findings from the EAE model may help to develop a molecular diagnosis for the early stage MScl in humans.

Application of metabolomics in autoimmune diseases: Insight into biomarkers and pathology

“…One of these metabolites-arginine was also identified by the targeted NMR method. Smolinska et al (2011) found that arginine, creatine and lysine changed in the CSF of EAE. Arginine involved pathways may be played in the onset of MS.…”

Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion

“…The experimental arrangement was as previously described by Smolinska et al and/or Hendricks [10, 11]. Here, we briefly summarize the main points.…”

“…Sampling, sample preparation, and acquisition of CSF NMR spectral data were as described elsewhere [11]. Blood was sampled intravenously by use of a heparin-treated syringe.…”

CHAPTER 3. High‐Resolution NMR‐Based Metabolic Profiling in Drug Discovery and Development

“…10 mL). 22 The metabolic profiles derived from the two models of either peripheral inflammation (induced by complete Freund adjuvant (CFA) emulsion) or neurological inflammation were compared using Partial Least Squares Discriminant Analysis (PLS-DA) and ANOVA Principal Component Analysis (ANOVA-PCA). Neurological inflammation was manifest in the experimental autoimmune/allergic encephalomyelitis (EAE) model, induced by CFA and myelin basic protein (MBP), which has become an important tool in the understanding of human disease given the resemblance in clinical expression and pathology to that of multiple sclerosis, although the neurodegeneration and demyelination processes are not mimicked in this model.…”