NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo
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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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HIF-1α plays a primary role in the negative regulation of PGC-1α.
“The hypoxia-inducible transcription factor HIF-1α plays a primary role in the negative regulation of PGC-1α [84].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [84]
Cites
Reversible middle cerebral artery occlusion without craniectomy in rats.
Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989) · Stroke · doi:10.1161/01.str.20.1.84 · Cited by 7,463 · see citing works
Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B., & Seeburg, P. H. (1994) · Neuron · doi:10.1016/0896-6273(94)90210-0 · Cited by 2,989 · see citing works
Benveniste, H., Drejer, J., Schousboe, A., & Diemer, N. H. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb05396.x · Cited by 2,863 · see citing works
Bederson, J. B., Pitts, L. H., Tsuji, M., Nishimura, M. C., Davis, R. L., & Bartkowski, H. (1986) · Stroke · doi:10.1161/01.str.17.3.472 · Cited by 2,681 · see citing works
Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders
Epstein, F. H., Lipton, S. A., & Rosenberg, P. A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199403033300907 · Cited by 2,644 · see citing works
Regulation of neuronal survival by the serine-threonine protein kinase Akt
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E. (1997) · Science · doi:10.1126/science.275.5300.661 · Cited by 2,436 · see citing works
Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., & Olney, J. W. (1999) · Science · doi:10.1126/science.283.5398.70 · Cited by 2,055 · see citing works
Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., & Lipton, S. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7162 · Cited by 1,958 · see citing works
Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
Hardingham, G. E., Fukunaga, Y., & Bading, H. (2002) · Nature Neuroscience · doi:10.1038/nn835 · Cited by 1,686 · see citing works
Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity
Liu, L., Wong, T. P., Pozza, M. F., Lingenhoehl, K., Wang, Y., Sheng, M., Auberson, Y. P., & Wang, Y. T. (2004) · Science · doi:10.1126/science.1096615 · Cited by 1,106 · see citing works
Self-citationThe changing landscape of ischaemic brain injury mechanisms
Lee, J.-M., Zipfel, G. J., & Choi, D. W. (1999) · Nature · doi:10.1038/399a007 · Cited by 1,102 · see citing works
Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation
Coffer, P. J., Jin, J., & Woodgett, J. R. (1998) · Biochemical Journal · doi:10.1042/bj3350001 · Cited by 1,067 · see citing works
Treatment of Ischemic Brain Damage by Perturbing NMDA Receptor- PSD-95 Protein Interactions
Aarts, M., Liu, Y., Liu, L.-D., Besshoh, S., Arundine, M., Gurd, J. W., Wang, Y.-T., Salter, M., & Tymianski, M. (2002) · Science · doi:10.1126/science.1072873 · Cited by 1,048 · see citing works
Self-citationXiong, Z., Zhu, X., Chu, X., Minami, M., Hey, J. G., Wei, W., MacDonald, J. F., Wemmie, J. A., Price, M. P., Welsh, M. J., et al. (2004) · Cell · doi:10.1016/j.cell.2004.08.026 · Cited by 1,026 · see citing works
Lu, W.-Y., Man, H.-Y., Ju, W., Trimble, W., Macdonald, J., & Wang, Y.-T. (2001) · Neuron · doi:10.1016/s0896-6273(01)00194-5 · Cited by 978 · see citing works
Self-citationN-methyl-D-aspartic acid receptor structure and function
McBain, C. J., & Mayer, M. L. (1994) · Physiological Reviews · doi:10.1152/physrev.1994.74.3.723 · Cited by 976 · see citing works
Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit
Sakimura, K., Kutsuwada, T., Ito, I., Manabe, T., Takayama, C., Kushiya, E., Yagi, T., Aizawa, S., Inoue, Y., Sugiyama, H., et al. (1995) · Nature · doi:10.1038/373151a0 · Cited by 859 · see citing works
Role of Distinct NMDA Receptor Subtypes at Central Synapses
Cull-Candy, S. G., & Leszkiewicz, D. N. (2004) · Science s STKE · doi:10.1126/stke.2552004re16 · Cited by 804 · see citing works
Tovar, K. R., & Westbrook, G. L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-10-04180.1999 · Cited by 786 · see citing works
A Key Role for TRPM7 Channels in Anoxic Neuronal Death
Aarts, M. M., Iihara, K., Wei, W.-L., Xiong, Z.-G., Arundine, M., Cerwinski, W., MacDonald, J. F., & Tymianski, M. (2003) · Cell · doi:10.1016/s0092-8674(03)01017-1 · Cited by 784 · see citing works
Self-citationHuettner, J. E., & Bean, B. P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1307 · Cited by 751 · see citing works
Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?
Ikonomidou, C., & Turski, L. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00164-3 · Cited by 727 · see citing works
Goldberg, M. P., & Choi, D. W. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-08-03510.1993 · Cited by 693 · see citing works
Massey, P. V., Johnson, B. E., Moult, P. R., Auberson, Y. P., Brown, M. W., Molnár, E., Collingridge, G. L., & Bashir, Z. I. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1697-04.2004 · Cited by 693 · see citing works
Gladstone, D., Black, S., & Hakim, A. (2002) · Stroke · doi:10.1161/01.str.0000025518.34157.51 · Cited by 685 · see citing works
Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury
Arundine, M., & Tymianski, M. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3319-x · Cited by 635 · see citing works
Self-citationHeyer, N. J., BITTNERJR, A., Echeverria, D., & WOODS, J. (2006) · Toxicology Letters · doi:10.1016/j.toxlet.2006.11.011 · Cited by 593 · see citing works
Chalecka-Franaszek, E., & Chuang, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8745 · Cited by 544 · see citing works
Lee, F. J. S., Xue, S., Pei, L., Vukusic, B., Chéry, N., Wang, Y., Wang, Y. T., Niznik, H. B., Yu, X.-M., & Liu, F. (2002) · Cell · doi:10.1016/s0092-8674(02)00962-5 · Cited by 542 · see citing works
Self-citationKutsuwada, T., Sakimura, K., Manabe, T., Takayama, C., Katakura, N., Kushiya, E., Natsume, R., Watanabe, M., Inoue, Y., Yagi, T., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80051-3 · Cited by 498 · see citing works
Kim, M. J., Dunah, A. W., Wang, Y. T., & Sheng, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.031 · Cited by 494 · see citing works
Self-citationFischer, G., Mutel, V., Trube, G., Malherbe, P., Kew, J. N. C., MOHACSI, E., Heitz, M., & Kemp, J. A. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37138-1 · Cited by 480 · see citing works
NMDA receptor pathways as drug targets
Kemp, J. A., & McKernan, R. M. (2002) · Nature Neuroscience · doi:10.1038/nn936 · Cited by 479 · see citing works
Mobile NMDA Receptors at Hippocampal Synapses
Tovar, K. R., & Westbrook, G. L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00658-x · Cited by 428 · see citing works
Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons
Stocca, G., & Vicini, S. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.013bu.x · Cited by 369 · see citing works
Ryck, M. D., Reempts, J. V., Borgers, M. J., Wauquier, A., & Janssen, P. A. J. (1989) · Stroke · doi:10.1161/01.str.20.10.1383 · Cited by 352 · see citing works
Ligand-Gated Ion Channel Interactions with Cytoskeletal and Signaling Proteins
Sheng, M., & Pak, D. T. S. (2000) · Annual Review of Physiology · doi:10.1146/annurev.physiol.62.1.755 · Cited by 348 · see citing works
Man, H., Wang, Q., Lu, W.-Y., Ju, W. H., Ahmadian, G., Liu, L., D’Souza, S. A., Wong, T. P., Taghibiglou, C., Lu, J., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00228-9 · Cited by 345 · see citing works
Self-citationCalcium and Excitotoxic Neuronal Injury
Choi, D. W. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb44407.x · Cited by 344 · see citing works
Clements, J. D., & Westbrook, G. L. (1991) · Neuron · doi:10.1016/0896-6273(91)90373-8 · Cited by 340 · see citing works
Lack of NMDA Receptor Subtype Selectivity for Hippocampal Long-Term Potentiation
Berberich, S., Punnakkal, P., Jensen, V., Pawlak, V., Seeburg, P. H., Hvalby, Ø., & Köhr, G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1905-05.2005 · Cited by 304 · see citing works
Synaptic and Extrasynaptic NMDA Receptor NR2 Subunits in Cultured Hippocampal Neurons
Thomas, C. G., Miller, A., & Westbrook, G. L. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00771.2005 · Cited by 286 · see citing works
Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons
Budd, S. L., Tenneti, L., Lishnak, T., & Lipton, S. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100121097 · Cited by 284 · see citing works
The problem of assessing effective neuroprotection in experimental cerebral ischemia
Corbett, D. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00078-6 · Cited by 278 · see citing works
Modulation of Triheteromeric NMDA Receptors by N-Terminal Domain Ligands
Hatton, C. J., & Paoletti, P. (2005) · Neuron · doi:10.1016/j.neuron.2005.03.005 · Cited by 237 · see citing works
Rap2-JNK Removes Synaptic AMPA Receptors during Depotentiation
Zhu, Y., Pak, D. T. S., Qin, Y., McCormack, S. G., Kim, M. J., Baumgart, J. P., Velamoor, V., Auberson, Y. P., Osten, P., Aelst, L. V., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.04.037 · Cited by 204 · see citing works
A Pilot Study of <scp>d</scp>-Cycloserine in Subjects With Autistic Disorder
Posey, D. J., Kem, D. L., Swiezy, N. B., Sweeten, T. L., Wiegand, R. E., & McDougle, C. J. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.2115 · Cited by 199 · see citing works
Zhou, M., & Baudry, M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4299-05.2006 · Cited by 196 · see citing works
Li, S., Tian, X.-J., Hartley, D., & Feig, L. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3990-05.2006 · Cited by 195 · see citing works
Calcium, free radicals and excitotoxins in neuronal apoptosis
Lipton, S. A., & Nicotera, P. (1998) · Cell Calcium · doi:10.1016/s0143-4160(98)90115-4 · Cited by 189 · see citing works
Köhr, G., Jensen, V., Koester, H. J., Mihaljević, A. L., Utvik, J. K., Kvello, A., Ottersen, O. P., Seeburg, P. H., Sprengel, R., & Hvalby, Ø. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10791.2003 · Cited by 181 · see citing works
Delayed Treatment with AMPA, but Not NMDA, Antagonists Reduces Neocortical Infarction
Xue, D., Huang, Z., Barnes, K., Lesiuk, H. J., Smith, K. E., & Buchan, A. M. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.32 · Cited by 177 · see citing works
Mutel, V., Buchy, D., Klingelschmidt, A., Messer, J., Bleuel, Z., Kemp, J. A., & Richards, J. G. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052147.x · Cited by 171 · see citing works
Weitlauf, C., Honse, Y., Auberson, Y. P., Mishina, M., Lovinger, D. M., & Winder, D. G. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2388-05.2005 · Cited by 170 · see citing works
Neuroprotective Signal Transduction: Relevance to Stroke
Mattson, M. P. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00010-3 · Cited by 144 · see citing works
Okamoto, S., Li, Z., Ju, C., Schölzke, M. N., Mathews, E. A., Cui, J., Salvesen, G. S., Bossy‐Wetzel, E., & Lipton, S. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022036399 · Cited by 138 · see citing works
Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells*
Chalovich, E. M., Zhu, J.-H., Caltagarone, J., Bowser, R., & Chu, C. T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602632200 · Cited by 108 · see citing works
Human Immunodeficiency Virus (HIV)-Induced Neurotoxicity: Roles for the NMDA Receptor Subtypes
O’Donnell, L. A., Agrawal, A., Jordan‐Sciutto, K. L., Dichter, M. A., Lynch, D. R., & Kolson, D. L. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4617-05.2006 · Cited by 104 · see citing works
Löschmann, P. A., de Groote, C., Smith, L. A., Wüllner, U., Fischer, G., Kemp, J. A., Jenner, P. G., & Klockgether, T. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.01.018 · Cited by 101 · see citing works
Short Therapeutic Window for MK-801 in Transient Focal Cerebral Ischemia in Normotensive Rats
Margaill, I., Parmentier, S., Callebert, J., Allix, M., Boulu, R. G., & Plotkine, M. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199601000-00013 · Cited by 88 · see citing works
Mielke, J. G., & Wang, Y. T. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02841.x · Cited by 87 · see citing works
Self-citationDeRidder, M. N., Simon, M. J., Siman, R., Auberson, Y. P., Raghupathi, R., & Meaney, D. F. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.10.011 · Cited by 87 · see citing works
Waxman, E. A., & Lynch, D. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502080200 · Cited by 78 · see citing works
Fast NMDA Receptor–Mediated Synaptic Currents in Neurons From Mice Lacking the ε2 (NR2B) Subunit
Tovar, K. R., Sprouffske, K., & Westbrook, G. L. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.1.616 · Cited by 70 · see citing works
Sarro, G. D., Siniscalchi, A., Ferreri, G., Gallelli, L., & Sarro, A. D. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00709-3 · Cited by 51 · see citing works
Mallon, A. P., Auberson, Y. P., & Stone, T. W. (2004) · Experimental Brain Research · doi:10.1007/s00221-004-2193-6 · Cited by 51 · see citing works
Wang, Y., Ju, W. H., Liu, L., Fam, S. R., D'Souza, S., Taghibiglou, C., Salter, M. W., & Wang, Y. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400199200 · Cited by 49 · see citing works
Self-citationControlling the Ups and Downs of Synaptic Strength
Bliss, T., & Schoepfer, R. (2004) · Science · doi:10.1126/science.1098805 · Cited by 41 · see citing works
Clements, J. D., & Westbrook, G. L. (1994) · Journal of Neurophysiology · doi:10.1152/jn.1994.71.6.2566 · Cited by 38 · see citing works
Tigaret, C. M., Thalhammer, A., Rast, G. F., Specht, C. G., Auberson, Y. P., Stewart, M. G., & Schoepfer, R. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.018580 · Cited by 37 · see citing works
Albensi, B. C., Igoechi, C., Janigro, D., & Ilkanich, E. V. (2004) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750401900502 · Cited by 31 · see citing works
Zoghbi, H. Y., Gage, F. H., & Choi, D. W. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00135-5 · Cited by 30 · see citing works
Chazot, P. L. (2000) · PubMed · Cited by 23 · see citing works
Wong, T. P., Liu, L., Sheng, M., & Wang, Y. T. (2004) · Science · doi:10.1126/science.1102399 · Cited by 21 · see citing works
Self-citationSignaling Events in NMDA Receptor‐Induced Apoptosis in Cerebrocortical Cultures
Budd, S. L., & Lipton, S. A. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07832.x · Cited by 16 · see citing works
Flagged first, then by citations
2 of the 77 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · see citing works
Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
Hardingham, G. E., & Bading, H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2911 · Cited by 1,644 · see citing works
Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells*
Chalovich, E. M., Zhu, J.-H., Caltagarone, J., Bowser, R., & Chu, C. T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602632200 · Cited by 108 · see citing works
Apoptotic Mechanisms After Cerebral Ischemia
Broughton, B. R. S., Reutens, D. C., & Sobey, C. G. (2009) · Stroke · doi:10.1161/strokeaha.108.531632 · Cited by 1,269 · see citing works
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106 · see citing works
Self-citationTraumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets
Ng, S. Y., & Lee, A. Y. W. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00528 · Cited by 864 · see citing works
Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications
Tuo, Q., Zhang, S., & Lei, P. (2021) · Medicinal Research Reviews · doi:10.1002/med.21817 · Cited by 747 · see citing works
Li, S., Jin, M., Koeglsperger, T., Shepardson, N. E., Shankar, G. M., & Selkoe, D. J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0203-11.2011 · Cited by 664 · see citing works
Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)
Zhao, Y., Zhang, X., Chen, X., & Wei, Y. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.5070 · Cited by 648 · see citing works
Pathogenic mechanisms following ischemic stroke
Khoshnam, S. E., Winlow, W., Farzaneh, M., Farbood, Y., & Moghaddam, H. F. (2017) · Neurological Sciences · doi:10.1007/s10072-017-2938-1 · Cited by 618 · see citing works
Astrocyte metabolism and signaling during brain ischemia
Rossi, D. J., Brady, J. D., & Mohr, C. (2007) · Nature Neuroscience · doi:10.1038/nn2004 · Cited by 558 · see citing works
Arnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
The Role of NMDA Receptors in Alzheimer’s Disease
Liu, J., Chang, L., Song, Y., Li, H., & Wu, Y. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00043 · Cited by 535 · see citing works
Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
Papadia, S., Soriano, F. X., Léveillé, F., Martel, M.-A., Dakin, K. A., Hansen, H. H., Kaindl, A., Sifringer, M., Fowler, J., Stefovska, V., et al. (2008) · Nature Neuroscience · doi:10.1038/nn2071 · Cited by 498 · see citing works
DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke
Tu, W., Xu, X., Peng, L., Zhong, X., Zhang, W., Soundarapandian, M. M., Belal, C., Wang, M., Jia, N., Zhang, W., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.055 · Cited by 493 · see citing works
Wang, M., Yang, Y., Wang, C.-J., Gamo, N. J., Jin, L. E., Mazer, J. A., Morrison, J. H., Wang, X.-J., & Arnsten, A. F. T. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.032 · Cited by 489 · see citing works
Synapses and Alzheimer's Disease
Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436 · see citing works
NMDA receptors in clinical neurology: excitatory times ahead
Kalia, L. V., Kalia, S. K., & Salter, M. W. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70165-0 · Cited by 417 · see citing works
Mony, L., Kew, J. N. C., Gunthorpe, M. J., & Paoletti, P. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00304.x · Cited by 404 · see citing works
Calcium‐dependent mitochondrial function and dysfunction in neurons
Pivovarova, N. B., & Andrews, S. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07754.x · Cited by 382 · see citing works
Raymond, L. A., André, V. M., Cepeda, C., Gladding, C. M., Milnerwood, A. J., & Levine, M. S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.052 · Cited by 319 · see citing works
Mechanism of differential control of NMDA receptor activity by NR2 subunits
Gielen, M. C., Retchless, B. S., Mony, L., Johnson, J. W., & Paoletti, P. (2009) · Nature · doi:10.1038/nature07993 · Cited by 325 · see citing works
Targeting NMDA receptors in stroke: new hope in neuroprotection
Wu, Q. J., & Tymianski, M. (2018) · Molecular Brain · doi:10.1186/s13041-018-0357-8 · Cited by 320 · see citing works
Self-citationBrown, C. E., Aminoltejari, K., Erb, H., Winship, I. R., & Murphy, T. H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4249-08.2009 · Cited by 319 · see citing works
NMDA receptors in nervous system diseases
Zhou, Q., & Sheng, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.030 · Cited by 293 · see citing works
Dysfunction of NMDA receptors in Alzheimer’s disease
Zhang, Y., Li, P., Feng, J., & Wu, M. (2016) · Neurological Sciences · doi:10.1007/s10072-016-2546-5 · Cited by 282 · see citing works
“Activation of GluN2A and decrease in GluN2B subunit may be an attempt to reduce A b induced neuronal dysfunction [52].”
BackgroundRauner, C., & Köhr, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.182600 · Cited by 270 · see citing works
Coupling of the NMDA receptor to neuroprotective and neurodestructive events
Hardingham, G. E. (2009) · Biochemical Society Transactions · doi:10.1042/bst0371147 · Cited by 260 · see citing works
Léveillé, F., Gaamouch, F. E., Gouix, E., Lecocq, M., Lobner, D., Nicole, O., & Buisson, A. (2008) · The FASEB Journal · doi:10.1096/fj.08-107268 · Cited by 258 · see citing works
Rönicke, R., Mikhaylova, M., Rönicke, S., Meinhardt, J., Schröder, U. H., Fändrich, M., Reiser, G., Kreutz, M. R., & Reymann, K. G. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.01.011 · Cited by 246 · see citing works
Differential Roles of NMDA Receptor Subtypes in Ischemic Neuronal Cell Death and Ischemic Tolerance
Chen, M., Lu, T., Chen, X., Zhou, Y., Chen, Q., Feng, X., Xu, L., Duan, W., & Xiong, Z. (2008) · Stroke · doi:10.1161/strokeaha.108.521898 · Cited by 242 · see citing works
Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke.
Shen, Z., Xiang, M., Chen, C., Ding, F., Wang, Y., Shang, C., Xin, L., Zhang, Y., & Cui, X.-N. (2022) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2022.113125 · Cited by 211 · see citing works
Self-citationKaindl, A. M., Degos, V., Peineau, S., Gouadon, E., Chhor, V., Loron, G., Charpentier, T. L., Josserand, J., Ali, C., Vivien, D., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23626 · Cited by 230 · see citing works
Tumor Necrosis Factor and Interleukin-1β Modulate Synaptic Plasticity during Neuroinflammation
Rizzo, F. R., Musella, A., Vito, F. D., Fresegna, D., Bullitta, S., Vanni, V., Guadalupi, L., Bassi, M. S., Buttari, F., Mandolesi, G., et al. (2018) · Neural Plasticity · doi:10.1155/2018/8430123 · Cited by 218 · see citing works
Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation
Fan, X., Wu, J., Lu, J., Wang, J., & Wang, Y. T. (2014) · Nature Neuroscience · doi:10.1038/nn.3637 · Cited by 213 · see citing works
Self-citationDysfunctional synapse in Alzheimer's disease – A focus on NMDA receptors
Mota, S. I., Ferreira, I. L., & Rego, A. C. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.08.013 · Cited by 206 · see citing works
Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices
Harris, A. Z., & Pettit, D. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.137679 · Cited by 202 · see citing works
Excitotoxicity: Still Hammering the Ischemic Brain in 2020
Choi, D. W. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.579953 · Cited by 198 · see citing works
Nakashima, A. S., & Dyck, R. H. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.10.003 · Cited by 199 · see citing works
Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function
Gladding, C. M., & Raymond, L. A. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.05.001 · Cited by 197 · see citing works
Coupling diverse routes of calcium entry to mitochondrial dysfunction and glutamate excitotoxicity
Stanika, R. I., Pivovarova, N. B., Brantner, C. A., Watts, C. A., Winters, C. A., & Andrews, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903546106 · Cited by 191 · see citing works
Ferreira, I. L., Bajouco, M., Mota, S. I., Auberson, Y. P., Oliveira, C. R., & Rego, A. C. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.11.008 · Cited by 185 · see citing works
Non‐synaptic receptors and transporters involved in brain functions and targets of drug treatment
Vizi, E. S., Fekete, Á., Károly, R., & Mike, Á. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00624.x · Cited by 182 · see citing works
Stroke intervention pathways: NMDA receptors and beyond
Lai, T. W., Shyu, W., & Wang, Y. T. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.12.008 · Cited by 177 · see citing works
Self-citationHackos, D. H., Lupardus, P. J., Grand, T., Chen, Y., Wang, T.-M., Reynen, P. H., Gustafson, A. E., Wallweber, H. J. A., Volgraf, M., Sellers, B. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.016 · Cited by 174 · see citing works
The Subtype of GluN2 C-terminal Domain Determines the Response to Excitotoxic Insults
Martel, M., Ryan, T. J., Bell, K. F. S., Fowler, J. H., McMahon, A., Al-Mubarak, B. R., Komiyama, N. H., Horsburgh, K. J., Kind, P. C., Grant, S. G. N., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.021 · Cited by 176 · see citing works
Multiple Defects in Energy Metabolism in Alzheimers Disease
Ferreira, I. L., Resende, R., Ferreiro, E. B., Rego, A. C., & Pereira, C. (2010) · Current Drug Targets · doi:10.2174/1389450111007011193 · Cited by 177 · see citing works
The Dichotomy of NMDA Receptor Signaling
Papadia, S., & Hardingham, G. E. (2007) · The Neuroscientist · doi:10.1177/10738584070130060401 · Cited by 175 · see citing works
Organization, control and function of extrasynaptic NMDA receptors
Papouin, T., & Oliet, S. H. R. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0601 · Cited by 172 · see citing works
The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology of Alzheimer’s Disease
Rudy, C. C., Hunsberger, H. C., Weitzner, D. S., & Reed, M. N. (2015) · Aging and Disease · doi:10.14336/ad.2014.0423 · Cited by 168 · see citing works
Fitting, S., Ignatowska-Jankowska, B. M., Bull, C., Skoff, R. P., Lichtman, A. H., Wise, L. E., Fox, M. A., Su, J., Medina, A. E., Krahe, T. E., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.026 · Cited by 162 · see citing works
Yu, S. P., Jiang, M. Q., Shim, S. S., Pourkhodadad, S., & Wei, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00636-1 · Cited by 165 · see citing works
Liu, S., Zhang, N., Guo, Y., Zhao, R., Shi, T., Feng, S., Wang, S.-Q., Yang, Q., Li, X., Wu, Y., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5828-11.2012 · Cited by 161 · see citing works
Safety and Efficacy of Transcranial Direct Current Stimulation in Acute Experimental Ischemic Stroke
Peruzzotti‐Jametti, L., Cambiaghi, M., Bacigaluppi, M., Gallizioli, M., Gaude, E., Mari, S., Sandrone, S., Cursi, M., Teneud, L., Comı, G., et al. (2013) · Stroke · doi:10.1161/strokeaha.113.001687 · Cited by 163 · see citing works
Specific Targeting of Pro-Death NMDA Receptor Signals with Differing Reliance on the NR2B PDZ Ligand
Soriano, F. X., Martel, M., Papadia, S., Vaslin, A., Baxter, P. S., Rickman, C., Forder, J. P., Tymianski, M., Duncan, R. R., Aarts, M. M., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1207-08.2008 · Cited by 156 · see citing works
Self-citationEmerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents
Khoshnam, S. E., Winlow, W., Farbood, Y., Moghaddam, H. F., & Farzaneh, M. (2017) · Journal of Stroke · doi:10.5853/jos.2016.01368 · Cited by 156 · see citing works
Ferreiro, E. B., Baldeiras, I., Ferreira, I. L., Costa, R. O., Rego, A. C., Pereira, C., & Oliveira, C. R. (2012) · International Journal of Cell Biology · doi:10.1155/2012/735206 · Cited by 152 · see citing works
Regulation of NMDA glutamate receptor functions by the GluN2 subunits
Vieira, M., Yong, X. L. H., Roche, K. W., & Anggono, V. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14970 · Cited by 151 · see citing works
SIK2 Is a Key Regulator for Neuronal Survival after Ischemia via TORC1-CREB
Sasaki, T., Takemori, H., Yagita, Y., Terasaki, Y., Uebi, T., Horike, N., Takagi, H., Susumu, T., Teraoka, H., Kusano, K.-I., et al. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.004 · Cited by 150 · see citing works
Role of NMDA Receptor-Mediated Glutamatergic Signaling in Chronic and Acute Neuropathologies
Carvajal, F. J., Mattison, H. A., & Cerpa, W. F. (2016) · Neural Plasticity · doi:10.1155/2016/2701526 · Cited by 150 · see citing works
Zhou, X., Ding, Q., Chen, Z., Yun, H., & Wang, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.482000 · Cited by 148 · see citing works
Martel, M., Wyllie, D. J. A., & Hardingham, G. E. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.080 · Cited by 149 · see citing works
NMDA and AMPA receptors dysregulation in Alzheimer's disease
Babaei, P. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174310 · Cited by 149 · see citing works
Plasticity and repair in the post-ischemic brain
Filippo, M. D., Tozzi, A., Costa, C., Belcastro, V., Tantucci, M., Picconi, B., & Calabresi, P. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.01.012 · Cited by 145 · see citing works
Wang, Y., Briz, V., Chishti, A. H., Bi, X., & Baudry, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3293-13.2013 · Cited by 143 · see citing works
Self-citationSynaptic NMDA Receptors Mediate Hypoxic Excitotoxic Death
Wroge, C. M., Hogins, J., Eisenman, L., & Mennerick, S. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6371-11.2012 · Cited by 142 · see citing works
Calcium Signaling in Synapse-to-Nucleus CommunicationPreprint
Hagenston, A. M., & Bading, H. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004564 · Cited by 140 · see citing works
Lipid rafts, synaptic transmission and plasticity: Impact in age-related neurodegenerative diseases
Sebastião, A. M., Colino-Oliveira, M., Assaife‐Lopes, N., Dias, R. B., & Ribeiro, J. A. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.053 · Cited by 128 · see citing works
Role of NMDA receptor–dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries
Taghibiglou, C., Martin, H. G. S., Lai, T. W., Cho, T., Prasad, S. S., Kojic, L., Lu, J., Liu, Y., Lo, E., Zhang, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2064 · Cited by 132 · see citing works
Self-citationEmerging mechanisms of disrupted cellular signaling in brain ischemia
Tymianski, M. (2011) · Nature Neuroscience · doi:10.1038/nn.2951 · Cited by 131 · see citing works
Self-citationKaufman, A. M., Milnerwood, A. J., Sepers, M. D., Coquinco, A., She, K., Wang, L., Lee, H., Craig, A. M., Cynader, M. S., & Raymond, L. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4129-11.2012 · Cited by 131 · see citing works
Self-citationMalko, P., & Jiang, L. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101755 · Cited by 128 · see citing works
Mechanisms of synaptic dysfunction and excitotoxicity in Huntington's disease
Sepers, M. D., & Raymond, L. A. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.02.006 · Cited by 127 · see citing works
Lozovaya, N., Gataullina, S., Tsintsadze, T. S., Tsintsadze, V., Pallesi‐Pocachard, E., Minlebaev, M., Goriounova, N. A., Buhler, E., Watrin, F., Shityakov, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms5563 · Cited by 123 · see citing works
Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity
Franchini, L., Carrano, N., Luca, M. D., & Gardoni, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041538 · Cited by 124 · see citing works
Vizi, E. S., Kisfali, M., & Lőrincz, T. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2012.10.005 · Cited by 123 · see citing works
Forder, J. P., & Tymianski, M. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.021 · Cited by 123 · see citing works
Self-citationHeng, M. Y., Detloff, P. J., Wang, P. L., Tsien, J. Z., & Albin, R. L. (2008) · Nature Precedings · doi:10.1523/jneurosci.5599-08.2009 · Cited by 123 · see citing works
Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance
Varela, E. V., Etter, G., & Williams, S. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.04.010 · Cited by 116 · see citing works
Báez, M. V., Cercato, M. C., & Jerusalinsky, D. A. (2018) · Neural Plasticity · doi:10.1155/2018/5093048 · Cited by 117 · see citing works
Stys, P. K., You, H., & Zamponi, G. W. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225276 · Cited by 115 · see citing works
Ren, Z., Pribiag, H., Jefferson, S. J., Shorey, M., Fuchs, T., Stellwagen, D., & Luscher, B. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.02.009 · Cited by 114 · see citing works
Zádori, D., Nyíri, G., Szőnyi, A., Szatmári, I., Fülöp, F., Toldi, J., Freund, T. F., Vécsei, L., & Klivènyi, P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0573-6 · Cited by 112 · see citing works
Tian, Z., Wang, Y., Zhang, N., Guo, Y., Feng, B., Liu, S., & Zhao, M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.04.011 · Cited by 110 · see citing works
Self-citationKim, H. J., Hwang, I. K., & Won, M. H. (2007) · Brain Research · doi:10.1016/j.brainres.2007.08.066 · Cited by 110 · see citing works
Alim, I., Teves, L. M., Li, R., Mori, Y., & Tymianski, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1729-13.2013 · Cited by 107 · see citing works
Self-citationZádori, D., Veres, G., Szalárdy, L., Klivènyi, P., & Vécsei, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170929 · Cited by 107 · see citing works
Huang, K., Kang, M. H., Askew, C. E., Kang, R., Sanders, S. S., Wan, J., Davis, N. G., & Hayden, M. R. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.027 · Cited by 107 · see citing works
Zhang, X.-L., Sullivan, J. A., Moskal, J. R., & Stanton, P. K. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.08.018 · Cited by 107 · see citing works
Ryan, T. J., Emes, R. D., Grant, S. G. N., & Komiyama, N. H. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-6 · Cited by 105 · see citing works
Mitochondrial Calcium Deregulation in the Mechanism of Beta-Amyloid and Tau Pathology
Esteras, N., & Abramov, A. Y. (2020) · Cells · doi:10.3390/cells9092135 · Cited by 104 · see citing works
Role of synaptic and nonsynaptic glutamate receptors in ischaemia induced neurotoxicity
Brassai, A., Suvanjeiev, R.-G., Bán, E.-G., & Lakatos, M. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2014.12.007 · Cited by 101 · see citing works
Neurotransmitters in the mediation of cerebral ischemic injury
Mayor, D., & Tymianski, M. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.050 · Cited by 102 · see citing works
Self-citationUncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects
Li, S.-X., Han, Y., Xu, L., Yuan, K., Zhang, R.-X., Sun, C.-Y., Xu, D.-F., Yuan, M., Deng, J.-H., Meng, S.-Q., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.85 · Cited by 100 · see citing works
Self-citationTissue-type plasminogen activator is a neuroprotectant in the mouse hippocampus
Echeverry, R., Wu, J., Haile, W. B., Guzman, J., & Yepes, M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41722 · Cited by 100 · see citing works
Zádori, D., Klivènyi, P., Szalárdy, L., Fülöp, F., Toldi, J., & Vécsei, L. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.06.004 · Cited by 98 · see citing works
Wang, X., & Zheng, W. (2019) · The FASEB Journal · doi:10.1096/fj.201801751r · Cited by 97 · see citing works
Gao, C., Gill, M. B., Tronson, N. C., Guedea, A. L., Guzmán, Y. F., Huh, K. H., Corcoran, K. A., Swanson, G. T., & Radulović, J. (2009) · Hippocampus · doi:10.1002/hipo.20705 · Cited by 96 · see citing works
Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury
Curcio, M., Salazar, I. L., Mele, M., Canzoniero, L. M. T., & Duarte, C. B. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.001 · Cited by 96 · see citing works
Olmo, I. G., Carvalho, T. G., Costa, V. V., Alves‐Silva, J., Ferrari, C. Z., Izidoro‐Toledo, T. C., da Silva, J., Teixeira, A. L., Souza, D. G., Marques, J. T., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01016 · Cited by 96 · see citing works
- Authors
- Liu, Y., Wong, T. P., Aarts, M., Rooyakkers, A., Liu, L., Lai, T. W., Wu, D. C., Lu, J., Tymianski, M., Craig, A. M., & Wang, Y. T.
- Affiliations
- University of British Columbia (CA)
- Toronto Western Hospital (CA)
- University of British Columbia Hospital (CA)
- Corresponding author
- Wang, Yu Tian
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-03-14
- Volume
- 27
- Issue
- 11
- Pages
- 2846-2857
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672582
- OpenAlex
- W2097095684
- Cited by
- 773
- References
- 77
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 22 · 2023: 30 · 2022: 23 · 2021: 51 · 2020: 43 · 2019: 35 · 2018: 44 · 2017: 39 · 2016: 50 · 2015: 39 · 2014: 58 · 2013: 48 · 2012: 72
- FWCI
- 18.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Heart and Stroke Foundation of British Columbia and Yukon
- Canadian Stroke Network
- Michael Smith Health Research BC
- Novartis Pharma
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- NMDA receptor subunits, NR2A, NR2B, excitotoxicity, ischemic stroke, neuronal apoptosis, neuroprotection, glycine, extrasynaptic NMDA receptors, synaptic NMDA receptors, infarct size, cortical cultures, focal cerebral ischemia, NMDA receptor antagonists
- MeSH terms
- Animals, Cells, Cultured, Brain Ischemia, Male, Mice, Transgenic, Neurons, Receptors, N-Methyl-D-Aspartate, Cell Death, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Protein Subunits, Mice, Rats
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