GABA and glutamate in the preterm neonatal brain: In-vivo measurement by magnetic resonance spectroscopy

• Published in: NeuroImage (Orlando, Fla.) Vol. 238; p. 118215
• Main Authors: Basu, Sudeepta K., Pradhan, Subechhya, du Plessis, Adre J., Ben-Ari, Yehezkel, Limperopoulos, Catherine
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021; Elsevier Limited; Elsevier
• Subjects: Autopsy; Brain; Brain - metabolism; Brain injury; Cognitive ability; gamma-Aminobutyric Acid - metabolism; Gestation; Glutamatergic transmission; Glutamic Acid - metabolism; Humans; Infant, Newborn; Infant, Premature - metabolism; Infants; Magnetic Resonance Spectroscopy; Medical imaging; Metabolism; Neonates; Neuroimaging; Neurons; Neurotransmitters; Newborn babies; Premature birth; Spectrum analysis; γ-Aminobutyric acid
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2021.118215

•GABA and glutamate play a crucial role in fetal neonatal brain development and injury.•1H-MRS GABA and glutamate measurement in the neonatal brain is challenging but feasible.•Guidelines are needed for optimization of neonatal j-difference editing studies.•We review the special considerations needed for interpretation of neonatal data.•Integration of multi-modal imaging with EEG will enhance functional understanding. Cognitive and behavioral disabilities in preterm infants, even without obvious brain injury on conventional neuroimaging, underscores a critical need to identify the subtle underlying microstructural and biochemical derangements. The gamma-aminobutyric acid (GABA) and glutamatergic neurotransmitter systems undergo rapid maturation during the crucial late gestation and early postnatal life, and are at-risk of disruption after preterm birth. Animal and human autopsy studies provide the bulk of current understanding since non-invasive specialized proton magnetic resonance spectroscopy (1H-MRS) to measure GABA and glutamate are not routinely available for this vulnerable population due to logistical and technical challenges. We review the specialized 1H-MRS techniques including MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS), special challenges and considerations needed for interpretation of acquired data from the developing brain of preterm infants. We summarize the limited in-vivo preterm data, highlight the gaps in knowledge, and discuss future directions for optimal integration of available in-vivo approaches to understand the influence of GABA and glutamate on neurodevelopmental outcomes after preterm birth.