Related Experiment Video
Updated: Sep 13, 2026
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Calcium-permeable AMPA receptors in neonatal hypoxic-ischemic encephalopathy (Review)
1Department of Neonatology, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215003, P.R. China.
Insights
Hypoxic-ischemic encephalopathy (HIE) causes newborn brain injury. This review highlights calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as key players in HIE brain damage.
Area of Science:
- Neuroscience
- Neonatal Medicine
- Pathophysiology
Background:
- Hypoxic-ischemic encephalopathy (HIE) is a significant cause of neonatal brain injury with severe long-term effects.
- Excitotoxicity, driven by excessive glutamate receptor (GluR) stimulation, is a primary mechanism of neuronal death during ischemia.
- While N-methyl-D-aspartic acid (NMDA) receptors were initially implicated, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are now recognized as critical mediators in HIE.
Purpose of the Study:
- To review the critical role of calcium-permeable AMPARs (Ca²⁺-AMPARs) in the pathogenesis of HIE.
- To explore the potential of targeting Ca²⁺-AMPARs for neuroprotective strategies in HIE.
Main Methods:
- Literature review focusing on the involvement of Ca²⁺-AMPARs in HIE.
- Analysis of studies investigating the mechanisms of AMPAR-mediated neurotoxicity in neonatal hypoxia-ischemia.
Main Results:
- Ca²⁺-AMPARs play a central role in the selective and delayed neuronal death observed in HIE.
- Excessive activation of Ca²⁺-AMPARs contributes significantly to brain damage following hypoxic-ischemic insults.
Conclusions:
- Ca²⁺-permeable AMPARs are crucial mediators of neuronal injury in HIE.
- Targeting Ca²⁺-AMPARs presents a promising therapeutic avenue for neuroprotection in newborns with HIE.
Abstract:
Hypoxic-ischemic encephalopathy (HIE) is an important cause of brain injury in the newborn and may result in long-term devastating consequences. Excessive stimulation of glutamate receptors (GluRs) is a pivotal mechanism underlying ischemia-induced selective and delayed neuronal death. Although initial studies focused on N-methyl-D-aspartic acid (NMDA) receptors as critical mediators in HIE, subsequent studies supported a more central role for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), particularly Ca2+-permeable AMPARs, in brain damage associated with hypoxia-ischemia. This study reviewed the important role of Ca2+-permeable AMPARs in HIE and the future potential neuroprotective strategies associated with Ca2+-permeable AMPARs.
