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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.

SUBMITTER: Wisnowski JL

PROVIDER: S-EPMC3582631 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.

Wisnowski Jessica L JL Blüml Stefan S Paquette Lisa L Zelinski Elizabeth E Nelson Marvin D MD Painter Michael J MJ Damasio Hanna H Gilles Floyd F Panigrahy Ashok A

PloS one 20130226 2

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., marke ...[more]

PMID: 23468888

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Project description:Individuals born very preterm (<32 weeks gestation) have altered brain growth and white matter maturation relative to their full-term peers, and approximately 30% will experience neurodevelopmental impairment. We investigated the relationship between neurodevelopmental impairment and MRI measures of white matter microstructure and brain volume. Children born before 30 weeks' gestation or who had very low birthweight (< 1500 g) underwent neurodevelopmental assessment and MRI at age 7 years as part of the PIANO study, a New Zealand-based cohort study. Fractional anisotropy (FA) and diffusivity measures were derived from diffusion tensor imaging to index white matter microstructure. Volumes were derived from T1-weighted imaging. Neurodevelopmental impairment was defined as a score < 85 on the Wechsler Intelligence Scale for Children, <5th centile on the Movement Assessment Battery for Children or a diagnosis of cerebral palsy by a paediatrician. Relationships between MRI and neurodevelopmental impairment were assessed with general linear models adjusted for sex, gestational age at birth, birthweight z-score, age at assessment, New Zealand Deprivation index score and multiplicity. Children with neurodevelopmental impairment (n = 38) had smaller total brain, cortical grey matter and cerebral white matter volumes compared to children without neurodevelopmental impairment (n = 62) (p < 0.05, false discovery rate corrected), but the regional volume differences did not remain significant after adjustment for total brain volume. Lower FA and higher radial diffusivity were observed in the superior longitudinal fasciculi, uncinate fasciculi and right hemisphere corticospinal tract in children with neurodevelopmental impairment. This may reflect differences in cellular properties such as myelination or axonal packing. Neurodevelopmental impairment may reflect smaller overall brain volume and altered microstructure in white matter tracts that are important for language, cognitive and motor functioning.

Dataset Information

Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.

Publications

Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.

Similar Datasets

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