{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:48:44Z","timestamp":1792198124075,"version":"4.4.0"},"reference-count":141,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172173"],"award-info":[{"award-number":["82172173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2025AFB173"],"award-info":[{"award-number":["2025AFB173"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke is a leading cause of global neurological mortality and disability, characterized by a complex pathogenesis wherein calcium overload constitutes a pivotal mechanism in neuronal and glial cell death. Following ischemia and reperfusion, excitotoxicity triggered by excessive glutamate release activates NMDA receptors and voltage-dependent calcium channels, leading to a large accumulation of intracellular Ca2+. This calcium dyshomeostasis subsequently initiates a cascade of detrimental events, including mitochondrial dysfunction, endoplasmic reticulum stress, reactive oxygen species generation, and the activation of calcium-dependent enzymes (such as calpain and phospholipase A2), ultimately culminating in cellular apoptosis or necrosis. In addition, calcium signaling imbalance is closely related to various forms of programmed cell death, such as ferroptosis and necroptosis. Research on calcium overload extends beyond neurons, with investigations in microglia and astrocytes yielding significant mechanistic insights. Although targeted interventions, encompassing calcium channel blockers, NMDA receptor antagonists, mitochondrial calcium homeostasis regulators, and calmodulin\/calmodulin kinase (CaM\/CaMK) inhibitors, have demonstrated preclinical progress, their clinical translation remains constrained. Future investigations should prioritize elucidating the nuanced regulatory mechanisms of calcium signaling pathways, developing highly selective and low-toxicity calcium intervention drugs, and combining multi-target treatment strategies such as neuroprotection, anti-inflammation, and tissue repair to provide theoretical basis and new solutions for the precise treatment of ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms27052279","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"2279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Mechanisms and Targeted Intervention Strategies of Calcium Overload in Ischemic Stroke"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0272-230X","authenticated-orcid":false,"given":"Yuwei","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-4741","authenticated-orcid":false,"given":"Qi","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Millenaar, D., Ragoschke-Schumm, A., Fehlmann, T., Raible, M., Lochner, P., B\u00f6hm, M., Fassbender, K., Keller, A., Mahfoud, F., and Ukena, C. (2022). Ischemic Stroke-A Scientometric Analysis. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.893121"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13167-024-00356-6","article-title":"The paradigm change from reactive medical services to 3PM in ischemic stroke: A holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation","volume":"15","author":"Golubnitschaja","year":"2024","journal-title":"EPMA J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pacinella, G., Ciaccio, A.M., and Tuttolomondo, A. (2024). Molecular Links and Clinical Effects of Inflammation and Metabolic Background on Ischemic Stroke: An Update Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13247515"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/S0140-6736(24)00933-4","article-title":"Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021","volume":"403","author":"Brauer","year":"2024","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ana.27105","article-title":"A Prospective Multicenter Analysis of Mobile Stroke Unit Cost-Effectiveness","volume":"97","author":"Rajan","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111225","DOI":"10.1016\/j.brainresbull.2025.111225","article-title":"Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology","volume":"221","author":"Mizoguchi","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref_7","first-page":"e41","article-title":"2025 Heart Disease and Stroke Statistics: A Report of US and Global Data from the American Heart Association","volume":"151","author":"Martin","year":"2025","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/med.22009","article-title":"Drugs\/agents for the treatment of ischemic stroke: Advances and perspectives","volume":"44","author":"Jia","year":"2024","journal-title":"Med. Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e076161","DOI":"10.1136\/bmj-2023-076161","article-title":"Advances in treatments for acute ischemic stroke","volume":"389","author":"Sharma","year":"2025","journal-title":"bmj"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175903","DOI":"10.1016\/j.ejphar.2023.175903","article-title":"The mechanisms of minocycline in alleviating ischemic stroke damage and cerebral ischemia-reperfusion injury","volume":"955","author":"Zhao","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Y.-W., Liu, Y., Luo, S.-Z., Huang, X.-J., Shen, Y., Wang, W.-S., and Lang, Z.-C. (2025). The significance of calcium ions in cerebral ischemia-reperfusion injury: Mechanisms and intervention strategies. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1585758"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s12013-024-01291-z","article-title":"A Comprehensive Fuzzy Model for Understanding Neuronal Calcium Distribution in Presence of VGCC, Na+\/Ca2+ Exchanger, Buffer, and ER Fluxes","volume":"82","author":"Jha","year":"2024","journal-title":"Cell Biochem. Biophys."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pikor, D., Hur\u0142a, M., S\u0142owikowski, B., Szymanowicz, O., Poszwa, J., Banaszek, N., Drelichowska, A., Jagodzi\u0144ski, P.P., Kozubski, W., and Dorszewska, J. (2024). Calcium Ions in the Physiology and Pathology of the Central Nervous System. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252313133"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122651","DOI":"10.1016\/j.lfs.2024.122651","article-title":"Exploring the intricacies of calcium dysregulation in ischemic stroke: Insights into neuronal cell death and therapeutic strategies","volume":"347","author":"Rahi","year":"2024","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hu, J., Zhu, Y., Pang, Z., Li, X., Zhang, H., Li, X., Gao, Y., Wang, Y., Li, P., and Zhou, Q. (2025). Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4\/CRT\/FA complex axis. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1531907"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117729","DOI":"10.1016\/j.bios.2025.117729","article-title":"Development of a label-free Ca2+ image sensor to visualize extracellular Ca2+ dynamics in the biological samples","volume":"287","author":"Parajuli","year":"2025","journal-title":"Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s12035-023-03581-8","article-title":"Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis","volume":"61","author":"Zhang","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6427","DOI":"10.4103\/jfmpc.jfmpc_1033_22","article-title":"Association of serum calcium levels with clinical severity of ischemic stroke at the time of admission as defined by NIHSS score: A cross-sectional, observational study","volume":"11","author":"Tripathi","year":"2022","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Meng, K., Lei, X., and He, D. (2024). Association between serum calcium and in-hospital mortality in intensive care unit patients with cerebral infarction: A cohort study. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1428868"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lu, Y., Ma, X., Tazmini, K., Yang, M., Zhou, X., and Wang, Y. (2022). Admission Serum Calcium Level and Short-Term Mortality After Acute Ischemic Stroke: A Secondary Analysis Based on a Norwegian Retrospective Cohort. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.889518"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fang, S., Huang, W., Qu, X., and Chai, W. (2024). The mitochondria as a potential therapeutic target in cerebral I\/R injury. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1500647"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1038\/s41598-025-88136-8","article-title":"Gen inhibiting the Wnt\/Ca2+ signaling pathway alleviates cerebral ischemia\/reperfusion injury","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152726","DOI":"10.1016\/j.tox.2021.152726","article-title":"Cadmium disrupts mitochondrial distribution and activates excessive mitochondrial fission by elevating cytosolic calcium independent of MCU-mediated mitochondrial calcium uptake in its neurotoxicity","volume":"453","author":"Tang","year":"2021","journal-title":"Toxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102783","DOI":"10.1016\/j.ceca.2023.102783","article-title":"Ca2+ signalling: A common language for organelles crosstalk in Parkinson\u2019s disease","volume":"115","author":"Peggion","year":"2023","journal-title":"Cell Calcium"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5529810","DOI":"10.1155\/2021\/5529810","article-title":"Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia-Reperfusion Injury","volume":"2021","author":"Zhu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Loh, K.W.Z., Liu, C., Soong, T.W., and Hu, Z. (2023). \u03b2 subunits of voltage-gated calcium channels in cardiovascular diseases. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1119729"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175874","DOI":"10.1016\/j.ejphar.2023.175874","article-title":"Amorphous selenium inhibits oxidative stress injury of neurons in vascular dementia rats by activating NMDAR pathway","volume":"955","author":"Zhu","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shkryl, V.M. (2024). Endoplasmic Reticulum Calcium Signaling in Hippocampal Neurons. Biomolecules, 14.","DOI":"10.3390\/biom14121617"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Pi\u00f1a, D.A., Rivera-Ram\u00edrez, N., Garc\u00eda-L\u00f3pez, G., D\u00edaz, N.F., and Molina-Hern\u00e1ndez, A. (2024). Calcium and Neural Stem Cell Proliferation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074073"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e202400009","DOI":"10.1002\/cbic.202400009","article-title":"Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells","volume":"25","author":"Pathiriparambath","year":"2024","journal-title":"Chembiochem"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neures.2022.09.013","article-title":"IP3R1-dependent astrocyte calcium signaling in chronic itch","volume":"187","author":"Tsuda","year":"2023","journal-title":"Neurosci. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e70110","DOI":"10.1002\/glia.70110","article-title":"STIM1-Dependent Calcium Signaling in Astrocytes Controls Glutamate Accumulation and Ischemic Brain Injury During Acute Stroke in Mice","volume":"74","author":"Choi","year":"2026","journal-title":"GLIA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liang, X., Cao, C., Liu, N., Chen, D., Liu, T., Ma, H., Liu, J., Wu, T., and Niu, J. (2025). Induced neural stem cells ameliorate blood-brain barrier injury by modulating the calcium signaling pathway of astrocyte in cerebral ischemia-reperfusion rats. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1611226"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eadn7577","DOI":"10.1126\/sciadv.adn7577","article-title":"Optogenetic calcium modulation in astrocytes enhances post-stroke recovery in chronic capsular infarct","volume":"11","author":"Cho","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102923","DOI":"10.1016\/j.ceca.2024.102923","article-title":"ER and SOCE Ca2+ signals are not required for directed cell migration in human iPSC-derived microglia","volume":"123","author":"Granzotto","year":"2024","journal-title":"Cell Calcium"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1161\/ATVBAHA.124.321141","article-title":"Cav\u03b23 Contributes to the Maintenance of the Blood-Brain Barrier and Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis","volume":"44","author":"Martus","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/cvr\/cvad126","article-title":"Activation of endothelial TRPM2 exacerbates blood-brain barrier degradation in ischemic stroke","volume":"120","author":"Zong","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00018-025-05804-8","article-title":"Piezo1 disrupts blood-brain barrier via CaMKII\/Nrf2 in ischemic stroke","volume":"82","author":"Fu","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13578-023-01126-z","article-title":"Damage mechanism and therapy progress of the blood-brain barrier after ischemic stroke","volume":"13","author":"Gao","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sonobe, T., and Kakinuma, Y. (2024). Non-neuronal cell-derived acetylcholine, a key modulator of the vascular endothelial function in health and disease. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1388528"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1161\/01.HYP.23.6.1113","article-title":"Cell-to-cell communication coordinates blood flow control","volume":"23","author":"Segal","year":"1994","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Negri, S., Scolari, F., Vismara, M., Brunetti, V., Faris, P., Terribile, G., Sancini, G., Berra-Romani, R., and Moccia, F. (2022). GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells. Cells, 11.","DOI":"10.3390\/cells11233860"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e154118","DOI":"10.1172\/JCI154118","article-title":"The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia","volume":"132","author":"Korte","year":"2022","journal-title":"J. Clin. Invest."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1152\/physrev.00041.2020","article-title":"Mitochondrial calcium exchange in physiology and disease","volume":"102","author":"Garbincius","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1016\/j.neuron.2022.03.021","article-title":"Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury","volume":"110","author":"Zong","year":"2022","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"155583","DOI":"10.1016\/j.phymed.2024.155583","article-title":"Salidroside derivative SHPL-49 attenuates glutamate excitotoxicity in acute ischemic stroke via promoting NR2A-CAMKII\u03b1-Akt\/CREB pathway","volume":"134","author":"Xie","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117272","DOI":"10.1016\/j.biopha.2024.117272","article-title":"Calpain: The regulatory point of cardiovascular and cerebrovascular diseases","volume":"179","author":"Zhang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11011-024-01470-0","article-title":"Selective inhibition of T-type calcium channel preserves ischemic pre-conditioning mediated neuroprotection during cerebral ischemia reperfusion injury in diabetic mice","volume":"40","author":"Sharma","year":"2024","journal-title":"Metab. Brain Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"117835","DOI":"10.1016\/j.ecoenv.2025.117835","article-title":"Role of calcium overload-mediated disruption of mitochondrial dynamics in offspring neurotoxicity due to methylmercury exposure during pregnancy and lactation","volume":"291","author":"Kong","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1038\/s41467-025-58737-y","article-title":"A TLK2-mediated calcium-driven cell death pathway links neuronal degeneration to nuclear envelope disruption","volume":"16","author":"Li","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37478","DOI":"10.1021\/acsami.2c10364","article-title":"Effect of Tetrahedral Framework Nucleic Acids on Neurological Recovery via Ameliorating Apoptosis and Regulating the Activation and Polarization of Astrocytes in Ischemic Stroke","volume":"14","author":"Zhou","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113125","DOI":"10.1016\/j.biopha.2022.113125","article-title":"Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke","volume":"151","author":"Shen","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neuroscience.2023.01.036","article-title":"Stromal Interaction Molecule 1-Mediated Store-Operated Calcium Entry Promotes Autophagy Through AKT\/Mammalian Target of Rapamycin Pathway in Hippocampal Neurons After Ischemic Stroke","volume":"514","author":"Zhang","year":"2023","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"goae066","DOI":"10.1093\/gastro\/goae066","article-title":"Research progress on the role of mitochondria in the process of hepatic ischemia-reperfusion injury","volume":"12","author":"Zhou","year":"2024","journal-title":"Gastroenterol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.freeradbiomed.2024.05.024","article-title":"MCU inhibition protects against intestinal ischemia-reperfusion by inhibiting Drp1-dependent mitochondrial fission","volume":"221","author":"Kadier","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"156505","DOI":"10.1016\/j.phymed.2025.156505","article-title":"6\u2032-O-caffeoylarbutin of Vaccinium dunalianum alleviated ischemic stroke through the PI3K\/AKT\/NF-\u03baB pathway","volume":"139","author":"Shi","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Novorolsky, R.J., Kasheke, G.D.S., Hakim, A., Foldvari, M., Dorighello, G.G., Sekler, I., Vuligonda, V., Sanders, M.E., Renden, R.B., and Wilson, J.J. (2023). Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: Novel opportunities for nanoparticle-based drug delivery. Front. Cell Neurosci., 17.","DOI":"10.3389\/fncel.2023.1226630"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1007\/s11033-025-10667-0","article-title":"Role of mitochondrial metabolism in ischemic stroke and natural products intervention","volume":"52","author":"Zhang","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1177\/0271678X251346277","article-title":"Deciphering the brain glucose metabolism: A gateway to innovative stroke therapies","volume":"45","author":"Pisani","year":"2025","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/jemt.24431","article-title":"Remote ischemic postconditioning alleviates cerebral ischemic injury through SERCA2\/endoplasmic reticulum stress-mediated apoptosis","volume":"87","author":"Chen","year":"2024","journal-title":"Microsc. Res. Tech."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101998","DOI":"10.1016\/j.xcrm.2025.101998","article-title":"TRPM2 overactivation drives hyperlipidemia-induced dysfunction of myeloid cells and neurovascular units","volume":"6","author":"Zong","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.2147\/JIR.S461795","article-title":"Microglia in Ischemic Stroke: Pathogenesis Insights and Therapeutic Challenges","volume":"17","author":"Shui","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1093\/brain\/awad401","article-title":"Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo","volume":"147","author":"Shrouder","year":"2024","journal-title":"Brain J. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e22788","DOI":"10.1096\/fj.202201426RR","article-title":"ADP-ribose transferase PARP16 mediated-unfolded protein response contributes to neuronal cell damage in cerebral ischemia\/reperfusion","volume":"37","author":"Wang","year":"2023","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1007\/s12975-025-01351-3","article-title":"Activation of ATF6 Signaling Confers Long-Term Beneficial Effects in Young and Aged Mice After Permanent Stroke","volume":"16","author":"Yu","year":"2025","journal-title":"Transl. Stroke Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1007\/s12975-022-01084-7","article-title":"Melatonin Offers Dual-Phase Protection to Brain Vessel Endothelial Cells in Prolonged Cerebral Ischemia-Recanalization Through Ameliorating ER Stress and Resolving Refractory Stress Granule","volume":"14","author":"Lu","year":"2023","journal-title":"Transl. Stroke Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.4103\/NRR.NRR-D-24-00630","article-title":"Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: Potential targets for neural repair in neurological diseases","volume":"20","author":"Peng","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jia, Z., Li, H., Xu, K., Li, R., Yang, S., Chen, L., Zhang, Q., Li, S., and Sun, X. (2024). MAM-mediated mitophagy and endoplasmic reticulum stress: The hidden regulators of ischemic stroke. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1470144"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3892\/mmr.2025.13636","article-title":"Role of mitochondrial Ca2+ in stroke: From molecular mechanism to treatment strategy (Review)","volume":"32","author":"Liu","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Rehman, S., Nadeem, A., Akram, U., Sarwar, A., Quraishi, A., Siddiqui, H., Malik, M.A.J., Nabi, M., Ul Haq, I., and Cho, A. (2024). Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040812"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7902","DOI":"10.7150\/thno.113396","article-title":"New insights into acute ischemic stroke from the perspective of spatial omics","volume":"15","author":"Deng","year":"2025","journal-title":"Theranostics"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Li, Y., Schappell, L.E., Polizu, C., DiPersio, J., Tsirka, S.E., Halterman, M.W., and Nadkarni, N.A. (2023). Evolving Clinical-Translational Investigations of Cerebroprotection in Ischemic Stroke. J. Clin. Med., 12.","DOI":"10.3390\/jcm12216715"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s10020-025-01212-7","article-title":"Calpain inhibition as a novel therapeutic strategy for aortic dissection with acute lower extremity ischemia","volume":"31","author":"Tan","year":"2025","journal-title":"Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"25565","DOI":"10.1021\/acsnano.4c06052","article-title":"Spatial Measurement and Inhibition of Calpain Activity in Traumatic Brain Injury with an Activity-Based Nanotheranostic Platform","volume":"18","author":"Madias","year":"2024","journal-title":"ACS Nano"},{"key":"ref_75","first-page":"101768","article-title":"Proteolysis of mitochondrial calpain-13 in cerebral ischemia-reperfusion injury","volume":"39","author":"Chukai","year":"2024","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1021\/acs.jcim.5c00258","article-title":"In Silico Screening for Small Molecules to Alter Calpain Proteolysis through Modulating Conformation Changes Induced by Heterodimerization","volume":"65","author":"Poudel","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1111\/bph.16425","article-title":"The mitochondrial calcium uniporter inhibitor Ru265 increases neuronal excitability and reduces neurotransmission via off-target effects","volume":"181","author":"Xu","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5064","DOI":"10.1039\/D4QI01102C","article-title":"Supramolecular delivery of dinuclear ruthenium and osmium MCU inhibitors","volume":"11","author":"Bigham","year":"2024","journal-title":"Inorg. Chem. Front."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114796","DOI":"10.1016\/j.intimp.2025.114796","article-title":"OPTN ameliorates chondrocyte apoptosis in temporomandibular joint osteoarthritis by modulating ER-mitochondria Ca2+ transfer","volume":"157","author":"Zhang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3892\/mmr.2022.12681","article-title":"Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke","volume":"25","author":"Wen","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12640-024-00726-y","article-title":"Curcumin Improves Hippocampal Cell Bioenergetics, Redox and Inflammatory Markers, and Synaptic Proteins, Regulating Mitochondrial Calcium Homeostasis","volume":"43","author":"Jara","year":"2025","journal-title":"Neurotox. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"111772","DOI":"10.1016\/j.celrep.2022.111772","article-title":"Essential role of the mitochondrial Na+\/Ca2+ exchanger NCLX in mediating PDE2-dependent neuronal survival and learning","volume":"41","author":"Rozenfeld","year":"2022","journal-title":"Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"101268","DOI":"10.1016\/j.omtm.2024.101268","article-title":"SERCA2a overexpression improves muscle function in a canine Duchenne muscular dystrophy model","volume":"32","author":"Kodippili","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4103\/NRR.NRR-D-24-00044","article-title":"Neuroserpin alleviates cerebral ischemia-reperfusion injury by suppressing ischemia-induced endoplasmic reticulum stress","volume":"21","author":"Liao","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"111331","DOI":"10.1016\/j.cellsig.2024.111331","article-title":"1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling","volume":"122","author":"Song","year":"2024","journal-title":"Cell Signal"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1021\/acschemneuro.3c00250","article-title":"Telaprevir Improves Memory and Cognition in Mice Suffering Ischemic Stroke via Targeting MALT1-Mediated Calcium Overload and Necroptosis","volume":"14","author":"Zhang","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13024-023-00636-1","article-title":"Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: Implications for preventive treatments of ischemic stroke and late-onset Alzheimer\u2019s disease","volume":"18","author":"Yu","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e202301762","DOI":"10.1002\/chem.202301762","article-title":"Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival in an in vitro Stroke Model","volume":"29","author":"Tortella","year":"2023","journal-title":"Chemistry"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Park, D.-J., Kang, J.-B., and Koh, P.-O. (2024). Epigallocatechin gallate improves neuronal damage in animal model of ischemic stroke and glutamate-exposed neurons via modulation of hippocalcin expression. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0299042"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s11064-022-03769-9","article-title":"Retinoic Acid Prevents the Neuronal Damage Through the Regulation of Parvalbumin in an Ischemic Stroke Model","volume":"48","author":"Kang","year":"2023","journal-title":"Neurochem. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111425","DOI":"10.1016\/j.isci.2024.111425","article-title":"Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity","volume":"27","author":"Pironet","year":"2024","journal-title":"iScience"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9562","DOI":"10.1007\/s12035-024-04184-7","article-title":"Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective","volume":"61","author":"Yang","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zong, P., Lin, Q., Feng, J., and Yue, L. (2022). A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death. Cells, 11.","DOI":"10.3390\/cells11030491"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11655-024-3669-9","article-title":"Kuanxiong Aerosol Attenuates Ischemic Stroke Injury via Modulation of the TRPV1 Channel","volume":"32","author":"Chen","year":"2025","journal-title":"Chin. J. Integr. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Shekhar, S., Liu, Y., Wang, S., Zhang, H., Fang, X., Zhang, J., Fan, L., Zheng, B., Roman, R.J., and Wang, Z. (2021). Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202101.0458.v1"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"110647","DOI":"10.1016\/j.biopha.2020.110647","article-title":"The Role of Transient Receptor Potential Channels in Blood-Brain Barrier Dysfunction after Ischemic Stroke","volume":"131","author":"Huang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"114728","DOI":"10.1016\/j.expneurol.2024.114728","article-title":"PI3K\u03b4 inhibition alleviates the brain injury during cerebral ischemia reperfusion via suppressing pericyte contraction in a TNF-\u03b1 dependent manner","volume":"375","author":"Qiu","year":"2024","journal-title":"Exp. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"a041763","DOI":"10.1101\/cshperspect.a041763","article-title":"The Roles of Transient Receptor Potential (TRP) Channels Underlying Aberrant Calcium Signaling in Blood-Retinal Barrier Dysfunction","volume":"17","author":"Dragoni","year":"2025","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"137192","DOI":"10.1016\/j.ijbiomac.2024.137192","article-title":"Mild photothermal activation of TRPV1 pathway for enhanced calcium ion overload therapy of hepatocellular carcinoma","volume":"282","author":"Yu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10863-023-09971-w","article-title":"Alpha-lipoic acid modulates the diabetes mellitus-mediated neuropathic pain via inhibition of the TRPV1 channel, apoptosis, and oxidative stress in rats","volume":"55","year":"2023","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Pichardo-Rojas, D., Pichardo-Rojas, P.S., Cornejo-Bravo, J.M., and Serrano-Medina, A. (2023). Memantine as a neuroprotective agent in ischemic stroke: Preclinical and clinical analysis. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1096372"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.4103\/1673-5374.390966","article-title":"Cav3.2 channel regulates cerebral ischemia\/reperfusion injury: A promising target for intervention","volume":"19","author":"Dai","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1111\/febs.17159","article-title":"Enhanced isradipine sensitivity in vascular smooth muscle cells due to hypoxia-induced Cav1.2 splicing and RbFox1\/Fox2 downregulation","volume":"291","author":"Poore","year":"2024","journal-title":"FEBS J."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kecsk\u00e9s, S., Menyh\u00e1rt, \u00c1., Bari, F., and Farkas, E. (2023). Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1175281"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/17460441.2023.2266994","article-title":"Calcium channel blockers\u2019 contribution to overcoming Current drug discovery challenges in Alzheimer\u2019s disease","volume":"19","author":"Bernard","year":"2024","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"116814","DOI":"10.1016\/j.bios.2024.116814","article-title":"A light-addressable potentiometric sensor-based extracellular calcium dynamic monitoring and imaging platform for cellular calcium channel drug evaluation","volume":"267","author":"Tian","year":"2025","journal-title":"Biosens. Bioelectron."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zhou, R., Lin, K., Leng, C., Zhou, M., Zhang, J., Li, Y., Liu, Y., Ye, X., Xu, X., and Sun, B. (2022). Chebulic Acid Prevents Hypoxia Insult via Nrf2\/ARE Pathway in Ischemic Stroke. Nutrients, 14.","DOI":"10.3390\/nu14245390"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sequeira, E., Pierce, M.L., Akasheh, D., Sellers, S., Gerwick, W.H., Baden, D.G., and Murray, T.F. (2020). Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke. Mar. Drugs, 18.","DOI":"10.3390\/md18070374"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Viejo, L., Rubio-Alarc\u00f3n, M., Arribas, R.L., Moreno-Castro, M., P\u00e9rez-Mar\u00edn, R., Braun-Cornejo, M., Estrada-Valencia, M., and de Los R\u00edos, C. (2021). Synthesis and Biological Assessment of 4,1-Benzothiazepines with Neuroprotective Activity on the Ca2+ Overload for the Treatment of Neurodegenerative Diseases and Stroke. Molecules, 26.","DOI":"10.3390\/molecules26154473"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13041-019-0533-5","article-title":"Excitotoxic glutamate causes neuronal insulin resistance by inhibiting insulin receptor\/Akt\/mTOR pathway","volume":"12","author":"Pomytkin","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Krasil\u2019nikova, I., Surin, A., Sorokina, E., Fisenko, A., Boyarkin, D., Balyasin, M., Demchenko, A., Pomytkin, I., and Pinelis, V. (2019). Insulin Protects Cortical Neurons Against Glutamate Excitotoxicity. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01027"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12028-022-01469-4","article-title":"Microglia Modulate Cortical Spreading Depolarizations After Ischemic Stroke: A Narrative Review","volume":"37","author":"Kearns","year":"2022","journal-title":"Neurocrit. Care"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"596","DOI":"10.2174\/1570159X18666200114160844","article-title":"Pre-clinical to Clinical Translational Failures and Current Status of Clinical Trials in Stroke Therapy: A Brief Review","volume":"18","author":"Dhir","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1474-4422(02)00164-3","article-title":"Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?","volume":"1","author":"Ikonomidou","year":"2002","journal-title":"Lancet Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e2456535","DOI":"10.1001\/jamanetworkopen.2024.56535","article-title":"Nelonemdaz and Patients with Acute Ischemic Stroke and Mechanical Reperfusion: The RODIN Randomized Clinical Trial","volume":"8","author":"Lee","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Saver, J.L., and Starkman, S. (2011). Magnesium in Clinical Stroke, University of Adelaide Press.","DOI":"10.1017\/UPO9780987073051.016"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1161\/01.STR.0000124458.98123.52","article-title":"Prehospital Neuroprotective Therapy for Acute Stroke","volume":"35","author":"Saver","year":"2004","journal-title":"Stroke"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1161\/STROKEAHA.124.048601","article-title":"Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial","volume":"56","author":"Ospel","year":"2024","journal-title":"Stroke"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S0140-6736(20)30258-0","article-title":"Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): A multicentre, double-blind, randomised controlled trial","volume":"395","author":"Hill","year":"2020","journal-title":"Lancet"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1056\/NEJMoa070240","article-title":"NXY-059 for the treatment of acute ischemic stroke","volume":"357","author":"Shuaib","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ghozy, S., Reda, A., Varney, J., Elhawary, A.S., Shah, J., Murry, K., Sobeeh, M.G., Nayak, S.S., Azzam, A.Y., and Brinjikji, W. (2022). Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.870141"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.3390\/ijms130911753","article-title":"Neuroprotection for stroke: Current status and future perspectives","volume":"13","author":"Minnerup","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1021\/acscentsci.8b00773","article-title":"A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia\/Reoxygenation Injury","volume":"5","author":"Woods","year":"2019","journal-title":"ACS Cent. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1177\/0271678X20908523","article-title":"The cell-permeable mitochondrial calcium uniporter inhibitor Ru265 preserves cortical neuron respiration after lethal oxygen glucose deprivation and reduces hypoxic\/ischemic brain injury","volume":"40","author":"Novorolsky","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"102281","DOI":"10.1016\/j.ceca.2020.102281","article-title":"Distinct pharmacological profiles of ORAI1, ORAI2, and ORAI3 channels","volume":"91","author":"Zhang","year":"2020","journal-title":"Cell Calcium"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"42","DOI":"10.5607\/en.2017.26.1.42","article-title":"Orai1 and Orai3 in Combination with Stim1 Mediate the Majority of Store-operated Calcium Entry in Astrocytes","volume":"26","author":"Kwon","year":"2017","journal-title":"Exp. Neurobiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/MNH.0000000000000967","article-title":"The TMEM16A channel as a potential therapeutic target in vascular disease","volume":"33","author":"Kaye","year":"2024","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"105702","DOI":"10.1016\/j.neuint.2024.105702","article-title":"Inhibition of piezo1 prevents chronic cerebral hypoperfusion-induced cognitive impairment and blood brain barrier disruption","volume":"175","author":"Xu","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Cisneros-Mejorado, A.J., P\u00e9rez-Samart\u00edn, A., Domercq, M., Arellano, R.O., Gottlieb, M., Koch-Nolte, F., and Matute, C. (2020). P2X7 Receptors as a Therapeutic Target in Cerebrovascular Diseases. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00092"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1186\/s12974-022-02601-z","article-title":"Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions","volume":"19","author":"Wilmes","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.neuropharm.2013.05.032","article-title":"P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation","volume":"73","author":"Eyo","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0140-6736(04)15490-1","article-title":"Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): Randomised controlled trial","volume":"363","author":"Muir","year":"2004","journal-title":"Lancet"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ibneur.2025.01.002","article-title":"Examining the therapeutic potential and side effects of calcium channel blockers in mortality and morbidity of patients with stroke: A systematic review of pre-clinical and clinical studies","volume":"18","author":"Hatamian","year":"2025","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1161\/01.STR.26.7.1183","article-title":"A randomized, double-blind, placebo-controlled pilot trial of intravenous magnesium sulfate in acute stroke","volume":"26","author":"Muir","year":"1995","journal-title":"Stroke"},{"key":"ref_135","first-page":"e001034","article-title":"Nerinetide Reduces Early Infarct Growth Among Stroke Patients Undergoing EVT Without Intravenous Alteplase","volume":"4","author":"Rex","year":"2024","journal-title":"Stroke Vasc. Interv. Neurol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1177\/0271678X241237159","article-title":"No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies","volume":"44","author":"Sun","year":"2024","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000528250","article-title":"Microcirculation No-Reflow Phenomenon after Acute Ischemic Stroke","volume":"86","author":"Hu","year":"2023","journal-title":"Eur. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/1570159X17666190927113021","article-title":"Nimodipine Reappraised: An Old Drug with a Future","volume":"18","author":"Carlson","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"15173","DOI":"10.1007\/s00210-025-04357-8","article-title":"Exploring NMDAR pathways in ischemic stroke: Implications for neurotoxic and neuroprotective mechanisms and therapeutic strategies","volume":"398","author":"Khan","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Egunlusi, A.O., and Joubert, J. (2024). NMDA Receptor Antagonists: Emerging Insights into Molecular Mechanisms and Clinical Applications in Neurological Disorders. Pharmaceuticals, 17.","DOI":"10.3390\/ph17050639"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1004127","DOI":"10.37349\/ent.2025.1004127","article-title":"The long-term neuroprotective effects of calcium (Ca2+) modulation in ischemic stroke: A systematic review from animal models","volume":"5","author":"Sasmita","year":"2025","journal-title":"Explor. Neuroprot. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:36:49Z","timestamp":1772689009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":141,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052279"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052279","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}