Excitotoxicity hypoxia-ischemia

Hypoxia-ischemia may initiate apoptosis in parallel with excitotoxicity 565 Triggers of ischemic apoptosis may include decreased supply or sensitivity to neurotrophins, oxidative stress, exposure to inflammatory cytokines or damage to mitochondria 566... 

Excitotoxicity leads to increased Ca2+ and Zn2+, which can activate cytotoxic intracellular pathways. The prolonged availability of extracellular glutamate during hypoxia-ischemia is transduced by neuronal membrane receptors into potentially lethal intracellular ionic derangements, in particular, intracellular Na+ and Ca2+ overload. Excitotoxic... 

Young C, Tenkova T, Dikranian K, Olney JW. 2004. Excitotoxic versus apoptotic mechanisms of neuronal cell death in perinatal hypoxia/ischemia. Curr Mol Med 4 77-85. 

Hypoxia/ischemia. Several lines of evidence suggest that anoxic or ischemic brain damage is mediated by an excitotoxic process. First, in hippocampal cell cultures, anoxic cell death is dependent on excitatory synaptic transmission and EAA antagonists protect against this damage (Rothman, 1984). Second, acute ischemia in vivo produces significant elevations of extracellular Glu and Asp in the rat hippocampus (Benveniste et al.,... 

The forces driving water flow to form cytotoxic edema are osmotic, generated in brain injury conditions (ischemia, trauma, hypoxia) by disturbances in ionic homeostasis due to failure of the Na /K+ ATPase and/or dramatic influx of Na" and Ca " via ionotropic glutamate receptors (excitotoxicity) and other ionic channels. These pathological alterations in cellular ionic homeostasis result in Na" " and water flow from the intravascular and extracellular space into the intracellular compartment. 

Excitotoxicity also plays a role in epileptic seizures and cerebral ischemia. During ischemic injury, a rapid accumulation of glutamate takes place. This induces a noxious Ca + influx into the cytoplasm. The Ca + conductance of NMDA receptors explains the efficacy of NMDA antagonists against hypoxic damage. In addition, AMPA antagonists have also a protective function in hypoxia (Siesjo et al., 1991)... 

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