Nmda Receptors And Ca2

Influx of calcium ions (Ca2+) following the activation of NMDA-sensitive glutamate receptors has been implicated in tolerance induction. NMDA induces tolerance against oxygen-glucose deprivation (OGD) in neuronal culture and organotypic hippocampal slices (50,51). Furthermore, NMDA-receptor antagonists prevent ischemic preconditioning in gerbils (52). A possible downstream mechanism of protection could be the Ca2+-triggered activation of cAMP-response-element-binding protein (CREB) (53), a transcription factor that induces genes known to protect neuronal cells from ischemic injury and promote neuronal survival (54). CREB phosphorylation is increased in gerbil hippocampal CA1 neurons after global ischemic preconditioning (52) and in surviving penumbral cells in a rat focal ischemic preconditioning model (55 ). NMDA-receptor activation has also been linked to the activation of nuclear factor-KB (NF-kB), another transcription factor implicated in neuroprotection (56 ).

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