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Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants
Jessica L Wisnowski1, Stefan Blüml, Lisa Paquette
1Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California, USA.
Insights
Glutamate excitotoxicity is linked to punctate white matter lesions in preterm infants. Magnetic resonance spectroscopy revealed altered glutamine levels, suggesting a potential biomarker for neuroprotection strategies against white matter injury.
Area of Science:
- Neuroscience
- Neonatology
- Biochemistry
Background:
- Preterm infants face high risks of neurodevelopmental disabilities.
- White matter injury during the neonatal period is a primary cause.
- Glutamate excitotoxicity is a suspected mechanism, but lacks in vivo evidence in preterm infants.
Purpose of the Study:
- To investigate alterations in glutamate and glutamine, markers of glutamatergic metabolism.
- To correlate these metabolic changes with punctate white matter lesions and diffuse excessive high signal intensity (DEHSI) in preterm infants.
Main Methods:
- Utilized magnetic resonance spectroscopy (MRS) on parietal white matter of 108 preterm infants.
- Independent evaluation of MRS studies for white matter injury patterns (punctate lesions and DEHSI).
- Quantified absolute concentrations of key metabolites, including glutamate and glutamine.
Main Results:
- Punctate white matter lesions showed a significant 29% increase in glutamine concentration (p=0.002).
- No significant changes in glutamatergic metabolism were observed with DEHSI.
- Severe DEHSI was associated with increased lactate, indicating tissue acidosis (p=0.001).
Conclusions:
- Findings support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions.
- Glutamate excitotoxicity may not be the primary mechanism in DEHSI.
- MRS serves as a valuable biomarker for identifying white matter injury pathogenesis in preterm infants, aiding timely neuroprotection.
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.
