Cellular Mechanisms of Intrapartum Hypoxic–Ischaemic Cerebral Injury
Cellular Mechanisms of Intrapartum Hypoxic–Ischaemic Cerebral Injury
The immature brain has a lower overall oxygen demand compared to the mature brain; however, regions undergoing active maturation have significantly higher oxygen needs.
High oxygen demands in actively maturing regions are critical for enzyme functions involved in neuronal development, ion homeostasis (e.g., Na K-ATPase), and oxidative metabolism.
Failure to meet regional energy demands during fetal asphyxia leads to rapid energy depletion, initiating cellular injury and cell death cascades.
Role of Glutamate in Brain Development and Injury
Glutamate is essential for normal neuronal development, including differentiation, dendritic arborization, synapse formation, and plasticity, primarily via NMDA receptors.
NMDA receptor activation under normal conditions tightly regulates calcium influx, crucial for neuronal growth and maturation.
Energy-dependent ion pumps maintain control over neuronal membrane potential, essential for normal glutamate receptor function.
In fetal asphyxia, energy failure disrupts glutamate regulation, leading to excessive presynaptic glutamate release and impaired reuptake, causing glutamate accumulation.
Sustained glutamate receptor activation leads to excessive calcium influx, triggering excitotoxic neuronal injury and cell death.