ABSTRACT
Glutamate excitotoxicity has been implicated in the pathogenesis of hypoxic brain injury. The N-methyl-D-aspartate (NMDA) receptor/channel-blocking drugs are effective agents for shutting down the electrical activity of the brain for a short period of time. The number of NMDA-type glutamate binding sites was assessed quantitatively using computerized densitometry of glutamate autoradiograms. The prototypic receptor/channel antagonist is dizocilpine, a large molecule that fits inside the channel. Because of the relatively enhanced neurotoxicity mediated by overstimulation of the NMDA receptor in the perinatal period, NMDA antagonists may be particularly effective for salvaging tissue from perinatal hypoxia-ischemia. In the cerebellum, where the Purkinje cells are very vulnerable, autoradiograms suggested that NMDA receptors were especially concentrated on the dendritic candelabra that receives excitatory input onto the Purkinje cells. The use of NMDA receptor antagonists clearly has promise as a neuroprotective strategy. The fact that dizocilpine and related agents are effective in animal models provides a starting point for the design of clinical protocols.
