title: Study of cytokine induced neuropathology by high resolution proton NMR spectroscopy of rat urine.
abstract: Multiple sclerosis is a major cause of non-traumatic neurological disability. The identification of markers that differentiate disease progression is critical to effective therapy. A combination of NMR spectroscopic metabolic profiling of urine and statistical pattern recognition was used to detect focal inflammatory central nervous system (CNS) lesions induced by microinjection of a replication-deficient recombinant adenovirus expressing TNF-alpha or IL1-beta cDNA into the brains of Wistar rats. These animals were compared with a group of naïve rats and a group of animals injected with an equivalent null adenovirus. Urine samples were collected 7 days after adenovirus injection, when the inflammatory lesion is maximally active. Principal components analysis and Partial Least Squares-Discriminate analysis of the urine (1)H NMR spectra revealed significant differences between each of the cytokine adenovirus groups and the control groups; for the TNF-alpha group the main differences lay in citrate and succinate, while for the IL-1beta group the predominant changes occurred in leucine, isoleucine, valine and myo-inositol. Thus, we can identify urinary metabolic vectors that not only separate rats with inflammatory lesions in the brain from control animals, but also distinguish between different types of CNS inflammatory lesions.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. jlg40@mole.bio.cam.ac.uk
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Campbell
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Fernando
authors.initials: F
authors.lastname: Pitossi
authors.forename: Peter
authors.initials: P
authors.lastname: Styles
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology*; D018076:DNA, Complementary; D003673:Defective Viruses / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology / Q000652:urine*; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology / Q000652:urine*
chemical_list: D018076:DNA, Complementary; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha