Calcium Transients in the Model of Rapidly Induced Anoxic Tolerance in Rat Cortical Slices: Involvement of NMDA Receptors

Abstract

In this study, we investigated the effects of NMDA receptor antagonists on calcium transients induced by a single 2-min preconditioning anoxia (PA) in rat olfactory cortical slices, and on the ability of PA to prevent pathological calcium overload induced by subsequent 10-min test anoxia (TA). Relative changes in the intracellular Ca²⁺ concentration (Ca_i) and in the level of Ca²⁺ bound to intracellular hydrophobic domains (Ca_b) were monitored using fura-2 and chlortetracycline, respectively. Our results confirmed that TA induces prominent long-lasting increases in Ca_i and Ca_b, reflecting cellular calcium overload. It was found that PA produces moderate increases in both Ca²⁺ pools and prevents Ca²⁺ overload induced by TA carried out 90 min later. Calcium transients and the protective effects of PA were significantly suppressed in slices treated with NMDA receptor antagonists during and 30 min after PA. These results indicate that moderate activation of the NMDA receptors participates in the mechanism of the PA-induced anoxic tolerance of cortical neurons.

Preconditioning of cortical neurons by oxygen-glucose deprivation: tolerance induction through abbreviated neurotoxic signaling

“…A different laboratory reports that reduced glutamate release may be an important mediator in similar models of preconditioning in cortical neurons (20). Reduced [glutamate] ex during otherwise lethal hypoxia is also noted in acute models of hypoxic preconditioning (28,56). Taken together, these findings indicate that reduced [glutamate] ex may represent a common end effector between different models of preconditioning.…”

“…Lethal OGD results in excessive levels of extracellular glutamate ([glutamate] ex ). A reduction in [glutamate] ex observed during otherwise lethal ischemia may represent a common end effector of divergent models and signaling pathways initiated by preconditioning (20,28,56). Cultures were subjected to NMDA preconditioning or nonpreconditioning wash, and 24 h later buffer was collected at the termination of 75-90 min of lethal OGD.…”

Elevated Synaptic Activity Preconditions Neurons against an in Vitro Model of Ischemia

“…Neurons can also be preconditioned by exposure to numerous environmental or chemical stimuli that generate "cross-tolerance" to ischemia (2). A key role for activation of the NMDA type of glutamate receptor during preconditioning by ischemia or OGD is well established (3)(4)(5)(6)(7)(8)(9)(10), although agreement is not complete (11,12). Moreover, transient non-lethal exposure to high dose glutamate or NMDA is sufficient on its own to also induce potent cross-tolerance to ischemia (13) or to OGD (1,6,14).…”

Original article Delayed preconditioning with NMDA receptor antagonists in a rat model of perinatal asphyxia

“…In particular the long list of preconditioning stressors includes hyperthermia, mild hypoxia and brief episodes of brain ischemia, as well as the application of different pharmacological compounds [13,73]. The role of activation of NMDA receptors in the mechanisms of inducing neuronal tolerance to hypoxia, ischemia and glutamatergic over-excitation has been repeatedly suggested [22,31,59,72]. These data seem to be consistent with the in vivo findings that (+)MK-801 inhibits ischemic preconditioning [6,33], although other data do not support these claims [15,71].…”