NMDA receptor and neonatal hypoxic brain injury

The NMDA-type glutamate receptor is a predominant mediator of excitotoxicit y in the immature brain due to overexpression of the receptor in the develo ping brain. Within the development period however, the extent of NMDA recep tor mediated processes including hypoxia-induced excitotoxicity may depend on the ontogeny of the NMDA receptor recognition and modulation sites, and subunits leading to altered function of the ion-channel comples. The functi on of the receptor may be modified by intracellular mechanisms such as phos phorylation/dephosphorylation, nitration, and generation of free radicals i ncluding nitric oxide. The susceptibility of the developing brain to hypoxi a depends on several factors: the lipid composition of the brain cell membr ane; the rate of membrane lipid peroxidation and the status of anti-oxidant defenses; the development and modulation of the NMDA receptor sites; the i ntracellular Ca2+ influx mechanisms; expression of apoptotic and antiapopto tic genes such as Bax and Bcl-2; and the activation of initiator caspases a nd caspase-3, the "executioner" of cell death. The developmental status of these cellular mechanisms and their response to hypoxia determine the fate of the hypoxic cell in the developing brain in the fetus and the newborn. ( C) 2001 Wiley-Liss, Inc.