ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 387 papers.
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Who cites it
387 citing papers in PubMed, 769 citations in OpenAlex.
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- Mechanism of Ammonia-Induced Brain Damage in Chinese Striped-Necked Turtle (Mauremys sinensis).Integrative zoology · 2026Article
- Negr1 deficiency alters glutamate signalling and kynurenine pathway in a mouse model of psychiatric disorders.Scientific reports · 2026Article
- GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities inScience advances · 2026Article
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Exploring NMDAR pathways in ischemic stroke: implications for neurotoxic and neuroprotective mechanisms and therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation.Neurochemical research · 2025Article
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Excitotoxic neuronal death requires superoxide entry into neurons through volume-regulated anion channels.Science advances · 2025Article
- How to Pick a Neuroprotective Drug in Stroke Without Losing Your Mind?Life (Basel, Switzerland) · 2025Review
- Factors Contributing to Resistance to Ischemia-Reperfusion Injury in Olfactory Mitral Cells.International journal of molecular sciences · 2025Review
- Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The diverse effects of ketamine, jack-of-all-trades: a narrative review.British journal of anaesthesia · 2025Review
- NP10679: A new horizon for neuroprotection in aneurysmal subarachnoid hemorrhage.The Journal of pharmacology and experimental therapeutics · 2025Article
- Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a non-human primate model of cytokine-Induced depression.Brain, behavior, and immunity · 2025Article
- Future Perspectives of NMDAR in CNS Disorders.Molecules (Basel, Switzerland) · 2025Review
- Association of concussion history with psychiatric symptoms, limbic system structure, and kynurenine pathway metabolites in healthy, collegiate-aged athletes.Brain, behavior, and immunity · 2025Article
- N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.Molecular neurobiology · 2025Article
327 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Well-documented experimental evidence from both in vitro and in vivo models of stroke strongly supports the critical involvement of NMDA receptor-mediated excitotoxicity in neuronal damage after stroke. Despite this, the results of clinical trials testing NMDA receptor antagonists as neuroprotectants after stroke and brain trauma have been discouraging. Here, we report that in mature cortical cultures, activation of either synaptic or extrasynaptic NR2B-containing NMDA receptors results in excitotoxicity, increasing neuronal apoptosis. In contrast, activation of either synaptic or extrasynaptic NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action against both NMDA receptor-mediated and non-NMDA receptor-mediated neuronal damage. A similar opposing action of NR2B and NR2A in mediating cell death and cell survival was also observed in an in vivo rat model of focal ischemic stroke. Moreover, we found that blocking NR2B-mediated cell death was effective in reducing infarct volume only when the receptor antagonist was given before the onset of stroke and not 4.5 h after stroke. In great contrast, activation of NR2A-mediated cell survival signaling with administration of either glycine alone or in the presence of NR2B antagonist significantly attenuated ischemic brain damage even when delivered 4.5 h after stroke onset. Together, the present work provides a molecular basis for the dual roles of NMDA receptors in promoting neuronal survival and mediating neuronal damage and suggests that selective enhancement of NR2A-containing NMDA receptor activation with glycine may constitute a promising therapy for stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.