title: Metabolomic analysis of cerebral spinal fluid from patients with severe brain injury.
abstract: Proton nuclear magnetic resonance (H-NMR) spectroscopic analysis of cerebral spinal fluid provides a quick, non-invasive modality for evaluating the metabolic activity of brain-injured patients. In a prospective study, we compared the CSF of 44 TBI patients and 13 non-injured control subjects. CSF was screened for ten parameters: β-glucose (Glu), lactate (Lac), propylene glycol (PG), glutamine (Gln), alanine (Ala), α-glucose (A-Glu), pyruvate (PYR), creatine (Cr), creatinine (Crt), and acetate (Ace). Using mixed effects measures, we discovered statistically significant differences between control and trauma concentrations (mM). TBI patients had significantly higher concentrations of PG, while statistical trends existed for lactate, glutamine, and creatine. TBI patients had a significantly decreased concentration of total creatinine. There were no significant differences between TBI patients and non-injured controls regarding β- or α-glucose, alanine, pyruvate or acetate. Correlational analysis between metabolites revealed that the strongest significant correlations in non-injured subjects were between β- and α-glucose (r = 0.74), creatinine and pyruvate (r = 0.74), alanine and creatine (r = 0.62), and glutamine and α-glucose (r = 0.60). For TBI patients, the strongest significant correlations were between lactate and α-glucose (r = 0.54), lactate and alanine (r = 0.53), and α-glucose and alanine (r = 0.48). The GLM and multimodel inference indicated that the combined metabolites of PG, glutamine, α-glucose, and creatinine were the strongest predictors for CMRO2, ICP, and GOSe. By analyzing the CSF of patients with TBI, our goal was to create a metabolomic fingerprint for brain injury.
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-7039, USA. tglenn@mednet.ucla.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Glenn
authors.forename: Daniel
authors.initials: D
authors.lastname: Hirt
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mendez
authors.forename: David L
authors.initials: DL
authors.lastname: McArthur
authors.forename: Rachael
authors.initials: R
authors.lastname: Sturtevant
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wolahan
authors.forename: Farbod
authors.initials: F
authors.lastname: Fazlollahi
authors.forename: Matthew
authors.initials: M
authors.lastname: Ordon
authors.forename: Arzu
authors.initials: A
authors.lastname: Bilgin-Freiert
authors.forename: Ben
authors.initials: B
authors.lastname: Ellingson
authors.forename: Paul
authors.initials: P
authors.lastname: Vespa
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D001930:Brain Injuries / Q000134:cerebrospinal fluid*; D005260:Female; D005947:Glucose / Q000134:cerebrospinal fluid; D006801:Humans; D007427:Intracranial Pressure; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D019946:Propylene Glycol / Q000134:cerebrospinal fluid*; D011522:Protons; D055815:Young Adult
chemical_list: D000596:Amino Acids; D011522:Protons; D019946:Propylene Glycol; D005947:Glucose