Excitotoxicity as a Common Mechanism for Fetal Neuronal Injury with Hypoxia and Intrauterine Inflammation.

Excitotoxicity as a Common Mechanism for Fetal Neuronal Injury with Hypoxia and Intrauterine Inflammation. Adv Pharmacol. 2016;76:85-101 Authors: Burd I, Welling J, Kannan G, Johnston MV Abstract Excitotoxicity is a mechanism of neuronal injury, implicated in the pathogenesis of many acute and chronic neurologic disorders, including perinatal brain injury associated with hypoxia-ischemia and exposure to intrauterine inflammation. Glutamate, the primary excitatory neurotransmitter, signals through N-methyl-d-aspartic acid (NMDA)/α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Proper functioning of both of these receptors, in conjunction with glutamate signaling, is crucial for normal development. However, even a small imbalance can result in perinatal neuronal injury. Therefore, a mechanistic understanding of the role of excitotoxicity and the NMDA/AMPA receptor functions is critical to establishing the pathogenesis of hypoxic-ischemic encephalopathy (HIE) and perinatal brain injury due to exposure to intrauterine inflammation. Evidence from experimental animal models and clinical studies indicates that both oxygen and glucose deficiencies play a major role in fetal neuronal injury. However, the connection between these deficiencies, excitotoxicity, and HIE is not well established. The excitotoxic mechanisms in animal models and humans have many parallels, suggesting that detailed animal studies can elicit clinical...
Source: Advances in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Adv Pharmacol Source Type: research