Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti‐stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor‐related compounds from showing efficacy in all clinical trials for ischemic stroke. In this perspective, the determination of therapeutic time windows of these kinds of compounds is useful in ensuring a therapeutic effect and accelerating clinical application. This mini‐review discussed the therapeutic time windows of compounds against NMDA receptors signaling pathways, described related influence factors and the status of clinical studies. The purpose of this review is to look for compounds with wide therapeutic time windows and better clinical application prospect.
Over the past decade, many studies have focused on clarifying the roles of different N-methyl-d-aspartate (NMDA) receptor subunits in cerebral ischemia, hoping to develop subunit-selective drugs. Recently, more attention was given to studying the role of GluN2C in ischemia damage, which may lead to the development of new NMDA receptor antagonists for cerebral ischemia. Results showed that GluN2C inhibition or knockout can effectively alleviate the ischemic injury caused by middle cerebral artery occlusion and, contrarily, can aggravate the damage to hippocampal CA1 circuit caused by transient global cerebral ischemia. These results indicate the complicated roles of GluN2C in cerebral ischemia. In this minireview, we focus on these findings, describe the roles of GluN2C from different cell origins in ischemic damage, and explain the above inconsistent experimental results. K E Y W O R D S astrocyte, cerebral ischemia, GluN2C, neuron, oligodendrocyte | 1189 DING et al.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.