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Glutamate signaling in the pathophysiology and therapy of prenatal insults

Irma E Holopainen1, Hanna B Laurén

  • 1Department of Pharmacology, Drug Development and Therapeutics, and Medicity Research Laboratory, Institute of Biomedicine University of Turku, Tykistökatu 6A, 4th floor, FIN-20014 Turku, Finland. irma.holopainen@utu.fi

Pharmacology, Biochemistry, and Behavior
|March 30, 2011
PubMed

Insights

Hypoxia-ischemia (HI) in premature infants selectively damages white matter, leading to periventricular leukomalasia and long-term neurodevelopmental deficits. Glutamate receptors (GluRs) contribute to this damage, suggesting potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Neonatalogy
  • Developmental Biology

Background:

  • Birth asphyxia and hypoxia-ischemia (HI) significantly impact central nervous system (CNS) development.
  • In premature infants, HI preferentially damages periventricular white matter (WM), causing periventricular leukomalasia (PVL) and subsequent neurodevelopmental issues like cerebral palsy.
  • Despite improved survival rates for low-birth-weight infants, a notable percentage experience lasting cognitive and behavioral deficits.

Purpose of the Study:

  • To review the role of excitatory glutamate receptors (GluRs) in oligodendrocyte (OL) damage following HI.
  • To explore therapeutic interventions targeting GluRs for HI-induced brain injury in neonates.

Main Methods:

  • Review of existing literature on developmental changes in glutamate receptor expression.
  • Analysis of experimental models and human infant data on HI-induced brain injury.
  • Discussion of therapeutic strategies targeting glutamate receptors.

Main Results:

  • Glutamate receptors (GluRs) play a critical role in oligodendrocyte (OL) damage in the context of HI.
  • HI-induced damage in the immature brain exhibits region-specific vulnerability, particularly in white matter.
  • Experimental models and human data indicate a link between GluRs and HI-related brain injury.

Conclusions:

  • Glutamate receptors (GluRs) are implicated in the pathogenesis of HI-induced white matter injury in preterm infants.
  • Targeting GluRs presents a potential therapeutic avenue for mitigating brain damage and improving outcomes in survivors of neonatal HI.
  • Further research into GluR-targeted therapies is warranted for clinical application in neonatal intensive care.

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