title: Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.
abstract: Preterm infants (∼10% of all births) are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS), we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and "diffuse excessive high signal intensity" (DEHSI), the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p = 0.002). In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p = 0.001), a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective.
authors.affiliation: Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Wisnowski
authors.forename: Stefan
authors.initials: S
authors.lastname: Blüml
authors.forename: Lisa
authors.initials: L
authors.lastname: Paquette
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zelinski
authors.forename: Marvin D
authors.initials: MD
authors.lastname: Nelson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Painter
authors.forename: Hanna
authors.initials: H
authors.lastname: Damasio
authors.forename: Floyd
authors.initials: F
authors.lastname: Gilles
authors.forename: Ashok
authors.initials: A
authors.lastname: Panigrahy
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002658:Developmental Disabilities / Q000209:etiology; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics
chemical_list: D018698:Glutamic Acid