Role of Excitatory Amino Acid Antagonists in the Management of Birth Asphyxia

Birth asphyxia is an important cause of permanent neuro-developmental disability. Asphyxia sets in course a progression of intracellular events which culminates in neuronal death, and this process may take up to 48 h to complete. Entry of calcium into the neurone appears to be the key to the cell death, and it is known that during asphyxia, excessive glutamate is released which stimulates the voltage-dependent N-methyl-D-aspartate (NMDA) receptor to open with an accumulation of excess intracellular calcium. MK-801 is a very effective NMDA receptor antagonist, and it has been shown that this drug prevents or significantly reduces the extent of cortical neurone infarction following experimental asphyxia in 7-day-old rat pups. Unfortunately, MK-801 is toxic to the pup, but newer NMDA receptor antagonists may offer the opportunity for neuroprotection in the human infant who has suffered severe birth asphyxia.