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This arterial obstruction leads to hypoxia and energy failure, culminating in primary brain damage. Although reperfusion is critical to salvage viable tissue, it often intensifies injury through oxidative stress, inflammation, and cell death\u2014a phenomenon called ischemia\u2013reperfusion (I\/R) injury. Milk fat globule-EGF factor 8 (MFG-E8), a multifunctional glycoprotein secreted by stem and immune cells, is a key regulator of inflammation and tissue repair. By modulating microglial activation, attenuating proinflammatory cytokine releases, and preserving neuronal integrity, MFG-E8 mitigates ischemia\u2013reperfusion injury and emerges as a novel therapeutic target for ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms26178708","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bridging Inflammation and Repair: The Promise of MFG-E8 in Ischemic Stroke Therapy"],"prefix":"10.3390","volume":"26","author":[{"given":"Ye-Jin","family":"Han","sequence":"first","affiliation":[{"name":"Laboratory of Neurosurgery, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea"},{"name":"Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosurgery, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea"},{"name":"Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Ho","family":"Geum","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-0538","authenticated-orcid":false,"given":"Jong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-9479","authenticated-orcid":false,"given":"Dong-Hyuk","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Neurosurgery, Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea"},{"name":"Department of Neurosurgery, Anam Hospital, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Stroke Collaborators (2021). Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the global burden of disease study 2019. Lancet Neurol., 20, 795\u2013820."},{"key":"ref_2","unstructured":"GBD 2021 Diseases and Injuries Collaborators (2024). Global incidhrence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u20132021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet, 403, 2133\u20132161."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9636897211023474","DOI":"10.1177\/09636897211023474","article-title":"Label-free quantitative proteome profiling of cerebrospinal fluid from a rat stroke model with stem cell therapy","volume":"30","author":"Hur","year":"2021","journal-title":"Cell Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1161\/STROKEAHA.117.017199","article-title":"Systematic review of the cost and cost-effectiveness of rapid endovascular therapy for acute ischemic stroke","volume":"48","author":"Sevick","year":"2017","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.18632\/aging.101931","article-title":"Aging and ischemic stroke","volume":"11","author":"Yousufuddin","year":"2019","journal-title":"Aging"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lanzer, P. (2013). Neurosurgery in Ischemic Stroke. PanVascular Medicine.","DOI":"10.1007\/978-3-642-37393-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1161\/01.STR.0000217418.29609.22","article-title":"Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: A systematic review","volume":"37","author":"Bandera","year":"2006","journal-title":"Stroke"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nian, K., Harding, I.C., Herman, I.M., and Ebong, E.E. (2020). Blood-brain barrier damage in ischemic stroke and its regulation by endothelial mechanotransduction. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.605398"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1706442","article-title":"Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct","volume":"378","author":"Nogueira","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1212\/CPJ.0b013e318296f0ec","article-title":"Standard strategies for acute ischemic stroke within the rtPA therapeutic window: Brazil","volume":"3","author":"Massaro","year":"2013","journal-title":"Neurol. Clin. Pract."},{"key":"ref_11","first-page":"185","article-title":"Thrombolysis and thrombectomy for acute ischemic stroke: Strengths and synergies","volume":"43","author":"Campbell","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ensci.2016.04.002","article-title":"Intravenous rtPA versus mechanical thrombectomy in acute ischemic stroke: A historical cohort in Joinville, Brazil","volume":"5","author":"Cabral","year":"2016","journal-title":"eNeurologicalSci"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1177\/1747493017743051","article-title":"Complications of endovascular treatment for acute ischemic stroke: Prevention and management","volume":"13","author":"Balami","year":"2018","journal-title":"Int. J. Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1136\/neurintsurg-2021-017349","article-title":"Stroke thrombectomy complication management","volume":"13","author":"Piechowiak","year":"2021","journal-title":"J. Neurointerv. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1161\/STR.0b013e318284056a","article-title":"Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"44","author":"Jauch","year":"2013","journal-title":"Stroke"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s41983-024-00790-3","article-title":"Factors predicting functional outcome after rtPA for patients with acute ischemic stroke","volume":"60","author":"Hamed","year":"2024","journal-title":"Egypt. J. Neurol. Psychiatry Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1161\/STROKEAHA.113.001938","article-title":"Good outcome rate of 35% in IV-tPA-treated patients with computed tomography angiography confirmed severe anterior circulation occlusive stroke","volume":"44","author":"Furie","year":"2013","journal-title":"Stroke"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e14825","DOI":"10.1111\/cns.14825","article-title":"Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator","volume":"30","author":"Huang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41582-021-00605-6","article-title":"Pharmacological brain cytoprotection in acute ischaemic stroke-renewed hope in the reperfusion era","volume":"18","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s41232-025-00372-7","article-title":"Neural repair mechanisms after ischemic stroke","volume":"45","author":"Irisa","year":"2025","journal-title":"Inflamm. Regen."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liaw, N., and Liebeskind, D. (2020). Emerging therapies in acute ischemic stroke. F1000Res, 9.","DOI":"10.12688\/f1000research.21100.1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"160","DOI":"10.5853\/jos.2019.00584","article-title":"tPA helpers in the treatment of acute ischemic stroke: Are they ready for clinical use?","volume":"21","author":"Kim","year":"2019","journal-title":"J. Stroke"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nm1735","article-title":"A new penumbra: Transitioning from injury into repair after stroke","volume":"14","author":"Lo","year":"2008","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Haupt, M., Gerner, S.T., B\u00e4hr, M., and Doeppner, T.R. (2023). Neuroprotective strategies for ischemic stroke-future perspectives. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054334"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3340\/jkns.2019.0188","article-title":"Milk fat globule-epidermal growth factor VIII ameliorates brain injury in the subacute phase of cerebral ischemia in an animal model","volume":"63","author":"Choi","year":"2020","journal-title":"J. Korean Neurosurg. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s13770-017-0093-7","article-title":"Current understanding of stem cell and secretome therapies in liver diseases","volume":"14","author":"Kim","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.neuropharm.2011.09.018","article-title":"Recombinant human MFG-E8 attenuates cerebral ischemic injury: Its role in anti-inflammation and anti-apoptosis","volume":"62","author":"Cheyuo","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/jid.2014.515","article-title":"Protective Effect of MFG-E8 after Cutaneous Ischemia\u2013Reperfusion Injury","volume":"135","author":"Uchiyama","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/eji.200940096","article-title":"Aberrant splicing of the milk fat globule-EGF factor 8 (MFG-E8) gene in human systemic lupus erythematosus","volume":"40","author":"Yamaguchi","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5628486","DOI":"10.1155\/2016\/5628486","article-title":"Functional role of milk fat globule-epidermal growth factor VIII in macrophage-mediated inflammatory responses and inflammatory\/autoimmune diseases","volume":"2016","author":"Yi","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s10495-011-0630-0","article-title":"Review: Milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation","volume":"16","author":"Aziz","year":"2011","journal-title":"Apoptosis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1517\/14728222.2013.829455","article-title":"Identification of MFG-E8 as a novel therapeutic target for diseases","volume":"17","author":"Li","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.3168\/jds.2024-25532","article-title":"Bioactive milk-derived nutrient MFG-E8 ameliorates skeletal muscle atrophy induced by mitochondria damage in aging rats via activating the MAPK\/ERK signaling pathway","volume":"108","author":"Guan","year":"2025","journal-title":"J. Dairy Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41420-020-00318-7","article-title":"MFG-E8 accelerates wound healing in diabetes by regulating \u201cNLRP3 inflammasome-neutrophil extracellular traps\u201d axis","volume":"6","author":"Huang","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1002\/ctm2.295","article-title":"Milk fat globule EGF factor 8 restores mitochondrial function via integrin-mediated activation of the FAK-STAT3 signaling pathway in acute pancreatitis","volume":"11","author":"Ren","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/1742-2094-9-148","article-title":"The neuroprotective effects of milk fat globule-EGF factor 8 against oligomeric amyloid \u03b2 toxicity","volume":"9","author":"Li","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1093\/molehr\/gaq102","article-title":"Expression of milk fat globule EGF-factor 8 (MFG-E8) mRNA and protein in the human endometrium and its regulation by prolactin","volume":"17","author":"Franchi","year":"2011","journal-title":"Mol. Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16886","DOI":"10.1073\/pnas.0508599102","article-title":"Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8","volume":"102","author":"Hanayama","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","unstructured":"Lui, F., Khan Suheb, M.Z., and Patti, L. (2025). Ischemic stroke. StatPearls, StatPearls Publishing LLC."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157015912803217341","article-title":"Post-stroke movement disorders: Clinical manifestations and pharmacological management","volume":"10","author":"Siniscalchi","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref_41","first-page":"tre-02","article-title":"Movement disorders after stroke in adults: A review","volume":"2","author":"Bansil","year":"2012","journal-title":"Tremor Other Hyperkinet. Mov."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995). Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med., 333, 1581\u20131587.","DOI":"10.1056\/NEJM199512143332401"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1161\/CIRCRESAHA.116.309278","article-title":"Acute ischemic stroke therapy overview","volume":"120","author":"Catanese","year":"2017","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/01.nrl.0000156205.66116.84","article-title":"Recombinant tissue plasminogen activator (rtPA) for stroke. The perspective at 8 years","volume":"11","author":"Frey","year":"2005","journal-title":"Neurologist"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1161\/STROKEAHA.110.592535","article-title":"Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: Real-world experience and a call for action","volume":"41","author":"Bhatia","year":"2010","journal-title":"Stroke"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/S0140-6736(16)00163-X","article-title":"Endovascular thrombectomy after large-vessel ischaemic stroke: A meta-analysis of individual patient data from five randomised trials","volume":"387","author":"Goyal","year":"2016","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Schaller, B. (2016). Excitotoxicity and Oxidative Stress in Acute Stroke. Ischemic Stroke\u2014Updates, IntechOpen.","DOI":"10.5772\/59738"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41392-022-01064-1","article-title":"Signaling pathways involved in ischemic stroke: Molecular mechanisms and therapeutic interventions","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_49","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_50","first-page":"264","article-title":"Resolution of inflammation and repair after ischemic brain injury","volume":"7","author":"Akihiko","year":"2020","journal-title":"Neuroimmunol. Neuroinflamm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Levinson, S., Pulli, B., and Heit, J.J. (2025). Neuroinflammation and acute ischemic stroke: Impact on translational research and clinical care. Front. Surg., 12.","DOI":"10.3389\/fsurg.2025.1501359"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1111\/jth.15336","article-title":"Thrombolytic strategies for ischemic stroke in the thrombectomy era","volume":"19","author":"Gauberti","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.pneurobio.2017.07.004","article-title":"Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms","volume":"158","author":"Stonesifer","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhang, C., Lan, X., Wang, Q., Zheng, Y., Cheng, J., Han, J., Li, C., Cheng, F., and Wang, X. (2025). Decoding ischemic stroke: Perspectives on the endoplasmic reticulum, mitochondria, and their crosstalk. Redox Biol., 82.","DOI":"10.1016\/j.redox.2025.103622"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1089\/ars.2010.3292","article-title":"Therapeutic targets for neuroprotection in acute ischemic stroke: Lost in translation?","volume":"14","author":"Stankowski","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Prescott, K., M\u00fcnch, A.E., Brahms, E., Weigel, M.K., Inoue, K., Buckwalter, M.S., Liddelow, S.A., and Peterson, T.C. (2023). Blocking of microglia-astrocyte proinflammatory signaling is beneficial following stroke. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1305949"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1097\/00004647-199710000-00006","article-title":"Reperfusion injury: Demonstration of brain damage produced by reperfusion after transient focal ischemia in rats","volume":"17","author":"Aronowski","year":"1997","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1749-6632.1994.tb36713.x","article-title":"Morphological manifestations of reperfusion injury in brain","volume":"723","author":"Dietrich","year":"1994","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_59","first-page":"199","article-title":"Reperfusion damage following focal ischemia: Pathophysiology and therapeutic windows","volume":"4","author":"Kuroda","year":"1997","journal-title":"Clin. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Garbuzova-Davis, S., Rodrigues, M.C., Hernandez-Ontiveros, D.G., Tajiri, N., Frisina-Deyo, A., Boffeli, S.M., Abraham, J.V., Pabon, M., Wagner, A., and Ishikawa, H. (2013). Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063553"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nn835","article-title":"Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways","volume":"5","author":"Hardingham","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/infdis\/jiv499","article-title":"Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4","volume":"213","author":"Li","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Shen, Z., Xiang, M., Chen, C., Ding, F., Wang, Y., Shang, C., Xin, L., Zhang, Y., and Cui, X. (2022). Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke. Biomed. Pharmacother., 151.","DOI":"10.1016\/j.biopha.2022.113125"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"52","DOI":"10.2174\/1871527320666210212141232","article-title":"Role of Calcium Homeostasis in Ischemic Stroke: A Review","volume":"21","author":"Ludhiadch","year":"2022","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: A triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13041-018-0357-8","article-title":"Targeting NMDA receptors in stroke: New hope in neuroprotection","volume":"11","author":"Wu","year":"2018","journal-title":"Mol. Brain"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"823","DOI":"10.2217\/fnl.11.55","article-title":"A new look at glutamate and ischemia: NMDA agonist improves long-term functional outcome in a rat model of stroke","volume":"6","author":"Dhawan","year":"2011","journal-title":"Future Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pneurobio.2013.11.006","article-title":"Excitotoxicity and stroke: Identifying novel targets for neuroprotection","volume":"115","author":"Lai","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S1474-4422(16)00114-9","article-title":"Neuroprotection in acute stroke: Targeting excitotoxicity, oxidative and nitrosative stress, and inflammation","volume":"15","author":"Chamorro","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"24151","DOI":"10.1074\/jbc.M113.482000","article-title":"Involvement of the GluN2A and GluN2B subunits in synaptic and extrasynaptic N-methyl-D-aspartate receptor function and neuronal excitotoxicity","volume":"288","author":"Zhou","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ladagu, A.D., Olopade, F.E., Adejare, A., and Olopade, J.O. (2023). GluN2A and GluN2B N-Methyl-D-aspartate receptor (NMDARs) subunits: Their roles and therapeutic antagonists in neurological diseases. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111535"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wan, G., and Bao, X. (2025). Extracellular vesicles as a potential therapy for stroke. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073130"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gu, C., Zhang, Q., Li, Y., Li, R., Feng, J., Chen, W., Ahmed, W., Soufiany, I., Huang, S., and Long, J. (2022). The PI3K\/AKT pathway-The potential key mechanisms of traditional Chinese medicine for stroke. Front. Med., 9.","DOI":"10.3389\/fmed.2022.900809"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ding, P.F., Zhang, H.S., Wang, J., Gao, Y.Y., Mao, J.N., Hang, C.H., and Li, W. (2022). Insulin resistance in ischemic stroke: Mechanisms and therapeutic approaches. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1092431"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1523\/JNEUROSCI.0455-06.2006","article-title":"Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability","volume":"26","author":"Soriano","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5256","DOI":"10.1074\/jbc.M008552200","article-title":"Akt activation protects hippocampal neurons from apoptosis by inhibiting transcriptional activity of p53","volume":"276","author":"Yamaguchi","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"E33","DOI":"10.1038\/10026","article-title":"How BAD phosphorylation is good for survival","volume":"1","author":"Downward","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1128\/MCB.21.3.893-901.2001","article-title":"Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1","volume":"21","author":"Kim","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10581","DOI":"10.1073\/pnas.1202810109","article-title":"Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death","volume":"109","author":"Jo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1073\/pnas.051634198","article-title":"Activity-dependent CREB phosphorylation: Convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway","volume":"98","author":"Wu","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0896-6273(02)00828-0","article-title":"Function and regulation of CREB family transcription factors in the nervous system","volume":"35","author":"Lonze","year":"2002","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0896-6273(02)00654-2","article-title":"Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV","volume":"34","author":"Impey","year":"2002","journal-title":"Neuron"},{"key":"ref_84","first-page":"1171","article-title":"NMDA-stimulated expression of BDNF mRNA in cultured cerebellar granule neurones","volume":"4","author":"Favaron","year":"1993","journal-title":"Neuroreport"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.nbd.2004.03.013","article-title":"Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain","volume":"16","author":"Hansen","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0896-6273(00)81011-9","article-title":"Identification of a signaling pathway involved in calcium regulation of BDNF expression","volume":"20","author":"Shieh","year":"1998","journal-title":"Neuron"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00001756-199206000-00004","article-title":"Photochemical stroke and brain-derived neurotrophic factor (BDNF) mRNA expression","volume":"3","author":"Comelli","year":"1992","journal-title":"Neuroreport"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1161\/STROKEAHA.108.521898","article-title":"Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance","volume":"39","author":"Chen","year":"2008","journal-title":"Stroke"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1126\/science.7522345","article-title":"Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase","volume":"265","author":"Huang","year":"1994","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3390\/antiox14080923","article-title":"The Mitochondrial Permeability Transition Pore in Platelets: Mechanisms, Physiological Roles, and Therapeutic Perspectives","volume":"14","author":"Lonobile","year":"2025","journal-title":"Antioxidants"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1523\/JNEUROSCI.5449-03.2004","article-title":"Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN","volume":"24","author":"Ning","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7997","DOI":"10.1523\/JNEUROSCI.5661-12.2013","article-title":"Critical role of increased PTEN nuclear translocation in excitotoxic and ischemic neuronal injuries","volume":"33","author":"Zhang","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1101\/gad.9.1.15","article-title":"Identification of a novel serine\/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death","volume":"9","author":"Deiss","year":"1995","journal-title":"Genes Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/sj.onc.1201172","article-title":"DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: Possible implications for role as tumor suppressor gene","volume":"15","author":"Kissil","year":"1997","journal-title":"Oncogene"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Wu, M., Xu, S., Mi, K., Yang, S., Xu, Y., Li, J., Chen, J., and Zhang, X. (2024). GluN2B-containing NMDA receptor attenuated neuronal apoptosis in the mouse model of HIBD through inhibiting endoplasmic reticulum stress-activated PERK\/eIF2\u03b1 signaling pathway. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1375843"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.brainres.2006.02.093","article-title":"Memantine, an uncompetitive low affinity NMDA open-channel antagonist improves clinical rating scores in a multiple infarct embolic stroke model in rabbits","volume":"1088","author":"Lapchak","year":"2006","journal-title":"Brain Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"924","DOI":"10.14336\/AD.2017.1126","article-title":"Mitochondria in ischemic stroke: New insight and implications","volume":"9","author":"Liu","year":"2018","journal-title":"Aging Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1161\/STROKEAHA.108.543769","article-title":"Mitochondrial targets for stroke: Focusing basic science research toward development of clinically translatable therapeutics","volume":"40","author":"Vosler","year":"2009","journal-title":"Stroke"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ab.2017.07.009","article-title":"Mitochondrial membrane potential","volume":"552","author":"Zorova","year":"2018","journal-title":"Anal. Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Huang, J., Chen, L., Yao, Z.M., Sun, X.R., Tong, X.H., and Dong, S.Y. (2023). The role of mitochondrial dynamics in cerebral ischemia-reperfusion injury. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114671"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Monsour, M., Gordon, J., Lockard, G., Alayli, A., and Borlongan, C.V. (2023). Mitochondria in cell-based therapy for stroke. Antioxidants, 12.","DOI":"10.3390\/antiox12010178"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1111\/cns.14344","article-title":"Intercellular mitochondrial transfer in the brain, a new perspective for targeted treatment of central nervous system diseases","volume":"29","author":"Geng","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Liu, Z., Sun, Y., Qi, Z., Cao, L., and Ding, S. (2022). Mitochondrial transfer\/transplantation: An emerging therapeutic approach for multiple diseases. Cell Biosci., 12.","DOI":"10.1186\/s13578-022-00805-7"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jointm.2023.02.002","article-title":"Oxidative stress as a bridge between age and stroke: A narrative review","volume":"3","author":"Feng","year":"2023","journal-title":"J. Intensive Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.3171\/foc.2007.22.5.3","article-title":"Cytotoxic edema: Mechanisms of pathological cell swelling","volume":"22","author":"Liang","year":"2007","journal-title":"Neurosurg. Focus"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12974-024-03033-7","article-title":"Mitochondrial stress: A key role of neuroinflammation in stroke","volume":"21","author":"Gao","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Mitroshina, E.V., Savyuk, M.O., Ponimaskin, E., and Vedunova, M.V. (2021). Hypoxia-inducible factor (HIF) in ischemic stroke and neurodegenerative disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.703084"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"105742","DOI":"10.1016\/j.phrs.2021.105742","article-title":"Hypoxia-inducible factor-1: Regulatory mechanisms and drug development in stroke","volume":"170","author":"Pan","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.2174\/092986709789760779","article-title":"Hypoxia inducible factor 1 as a therapeutic target in ischemic stroke","volume":"16","author":"Shi","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhang, X., Xiong, X., Zhu, H., Chen, R., Zhang, S., Chen, G., and Jian, Z. (2022). Nrf2 regulates oxidative stress and its role in cerebral ischemic stroke. Antioxidants, 11.","DOI":"10.3390\/antiox11122377"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.cellsig.2014.04.003","article-title":"Reduced phosphorylation of Stat3 at Ser-727 mediated by casein kinase 2-protein phosphatase 2A enhances Stat3 Tyr-705 induced tumorigenic potential of glioma cells","volume":"26","author":"Mandal","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1161\/STROKEAHA.111.626648","article-title":"Neuroprotection by interleukin-6 is mediated by signal transducer and activator of transcription 3 and antioxidative signaling in ischemic stroke","volume":"42","author":"Jung","year":"2011","journal-title":"Stroke"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"tkad018","DOI":"10.1093\/burnst\/tkad018","article-title":"Targeting neuronal mitophagy in ischemic stroke: An update","volume":"11","author":"Li","year":"2023","journal-title":"Burn. Trauma"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6232902","DOI":"10.1155\/2022\/6232902","article-title":"Role of mitophagy in the pathogenesis of stroke: From mechanism to therapy","volume":"2022","author":"Zhong","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.4103\/1673-5374.274331","article-title":"Autophagy and inflammation in ischemic stroke","volume":"15","author":"Mo","year":"2020","journal-title":"Neural. Regen. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"113684","DOI":"10.1016\/j.expneurol.2021.113684","article-title":"An updated review of autophagy in ischemic stroke: From mechanisms to therapies","volume":"340","author":"Wang","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13041-025-01201-1","article-title":"Role of autophagy in neurotoxic protein\u2019s clearance following post-ischemic stroke: Where we are and what we know?","volume":"18","author":"Kazmi","year":"2025","journal-title":"Mol. Brain"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"109839","DOI":"10.1016\/j.cellsig.2020.109839","article-title":"Orexin-A protects against cerebral ischemia-reperfusion injury by inhibiting excessive autophagy through OX1R-mediated MAPK\/ERK\/mTOR pathway","volume":"79","author":"Xu","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.bbamcr.2007.03.010","article-title":"p38 MAP-kinases pathway regulation, function and role in human diseases","volume":"1773","author":"Cuenda","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"17562864231187770","DOI":"10.1177\/17562864231187770","article-title":"mTOR pathway\u2014A potential therapeutic target in stroke","volume":"16","author":"Melanis","year":"2023","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.biopha.2018.01.067","article-title":"Vitexin reverses the autophagy dysfunction to attenuate MCAO-induced cerebral ischemic stroke via mTOR\/Ulk1 pathway","volume":"99","author":"Jiang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Xu, F., Li, J., Ni, W., Shen, Y.W., and Zhang, X.P. (2013). Peroxisome proliferator-activated receptor-\u03b3 agonist 15d-prostaglandin J2 mediates neuronal autophagy after cerebral ischemia-reperfusion injury. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055080"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"5544","DOI":"10.3892\/ijmm.2025.5544","article-title":"Molecular mechanisms of programmed cell death and potential targeted pharmacotherapy in ischemic stroke (Review)","volume":"56","author":"Duan","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Shu, J., Yang, L., Wei, W., and Zhang, L. (2022). Identification of programmed cell death-related gene signature and associated regulatory axis in cerebral ischemia\/reperfusion injury. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.934154"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/jnc.13028","article-title":"TNF\u03b1 in cerebral ischemia: Another stroke against you?","volume":"132","author":"Wilkins","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/sj.emboj.7600039","article-title":"Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific","volume":"23","author":"Ho","year":"2004","journal-title":"EMBO J."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wang, Y., Cao, Y., Zhu, Q., Gu, X., and Zhu, Y.Z. (2016). The discovery of a novel inhibitor of apoptotic protease activating factor-1 (Apaf-1) for ischemic heart: Synthesis, activity and target identification. Sci. Rep., 6.","DOI":"10.1038\/srep29820"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S1097-2765(01)00214-3","article-title":"PUMA, a novel proapoptotic gene, is induced by p53","volume":"7","author":"Nakano","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/cr.2008.62","article-title":"p53\u2019s mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity","volume":"18","author":"Wolff","year":"2008","journal-title":"Cell Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s12264-010-1111-0","article-title":"p53-mediated neuronal cell death in ischemic brain injury","volume":"26","author":"Hong","year":"2010","journal-title":"Neurosci. Bull."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1177\/0271678X17715956","article-title":"Interplay between Notch and p53 promotes neuronal cell death in ischemic stroke","volume":"38","author":"Balaganapathy","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pneurobio.2018.03.002","article-title":"Notch signaling and neuronal death in stroke","volume":"165\u2013167","author":"Arumugam","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Green, D.R. (2022). Nonapoptotic cell death pathways. Cold Spring Harb. Perspect. Biol., 14.","DOI":"10.1101\/cshperspect.a041103"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Hao, W., and Feng, C. (2023). Research progress on pyroptosis and its effect on the central nervous system. Neurobiol. Dis., 188.","DOI":"10.1016\/j.nbd.2023.106333"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"111065","DOI":"10.1016\/j.brainresbull.2024.111065","article-title":"The role of glutathione peroxidase 4 in neuronal ferroptosis and its therapeutic potential in ischemic and hemorrhagic stroke","volume":"217","author":"Wei","year":"2024","journal-title":"Brain Res. Bull."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1113\/jphysiol.2011.210294","article-title":"Targeting the Nrf2-Keap1 antioxidant defence pathway for neurovascular protection in stroke","volume":"589","author":"Alfieri","year":"2011","journal-title":"J. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1742-2094-5-45","article-title":"TNF signaling inhibition in the CNS: Implications for normal brain function and neurodegenerative disease","volume":"5","author":"McCoy","year":"2008","journal-title":"J. Neuroinflamm."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Yli-Karjanmaa, M., Clausen, B.H., Degn, M., Novrup, H.G., Ellman, D.G., Toft-Jensen, P., Szymkowski, D.E., Stensballe, A., Meyer, M., and Brambilla, R. (2019). Topical administration of a soluble TNF inhibitor reduces infarct volume after focal cerebral ischemia in mice. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00781"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Lu, W., Chen, Z., and Wen, J. (2024). Flavonoids and ischemic stroke-induced neuroinflammation: Focus on the glial cells. Biomed. Pharmacother., 170.","DOI":"10.1016\/j.biopha.2023.115847"},{"key":"ref_140","first-page":"294","article-title":"Cytokines: Their role in stroke and potential use as biomarkers and therapeutic targets","volume":"5","author":"Doll","year":"2014","journal-title":"Aging Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cytogfr.2024.06.002","article-title":"The impact of cytokines in neuroinflammation-mediated stroke","volume":"78","author":"Kumari","year":"2024","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Geng, H., Chen, L., Tang, J., Chen, Y., and Wang, L. (2022). The role of CCL2\/CCR2 axis in cerebral ischemia-reperfusion injury and treatment: From animal experiments to clinical trials. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073485"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"115192","DOI":"10.1016\/j.expneurol.2025.115192","article-title":"CCL2\/CCR2 signaling-mediated microglial migration leads to cerebral small vessel dysfunction in chronic hypertension model rats","volume":"387","author":"Koizumi","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41423-023-01032-x","article-title":"New genetic and epigenetic insights into the chemokine system: The latest discoveries aiding progression toward precision medicine","volume":"20","author":"Xu","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"ref_145","first-page":"703","article-title":"Current status and future prospects in HMGB1 and receptor researches","volume":"74","author":"Takahashi","year":"2016","journal-title":"Nihon Rinsho."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1742-2094-8-140","article-title":"LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury","volume":"8","author":"Vartanian","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00204-015-1472-2","article-title":"Compromised MAPK signaling in human diseases: An update","volume":"89","author":"Kim","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12031-016-0717-8","article-title":"The mitogen-activated protein kinase (MAPK) signaling pathway as a discovery target in stroke","volume":"59","author":"Sun","year":"2016","journal-title":"J. Mol. Neurosci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1161\/01.STR.0000083051.93319.28","article-title":"Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion","volume":"34","author":"Pfefferkorn","year":"2003","journal-title":"Stroke"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.3171\/foc.2007.22.5.5","article-title":"Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia","volume":"22","author":"Rosenberg","year":"2007","journal-title":"Neurosurg. Focus"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1567202614666161104114821","article-title":"Hypoxic preconditioning increases blood-brain barrier disruption in the early stages of cerebral ischemia","volume":"14","author":"Chi","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, H., Li, X., Wu, J., Xue, T., Wu, J., Shen, H., Li, X., Shen, M., and Chen, G. (2020). TMEM16F aggravates neuronal loss by mediating microglial phagocytosis of neurons in a rat experimental cerebral ischemia and reperfusion model. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01144"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1523\/JNEUROSCI.2620-14.2015","article-title":"Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experimental stroke","volume":"35","author":"Kawabori","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1111\/j.1462-5822.2007.00981.x","article-title":"Macrophage complement receptors and pathogen clearance","volume":"9","author":"Wiesmann","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"429","DOI":"10.14336\/AD.2019.0119","article-title":"Significance of complement system in ischemic stroke: A comprehensive review","volume":"10","author":"Ma","year":"2019","journal-title":"Aging Dis."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"8417","DOI":"10.1073\/pnas.87.21.8417","article-title":"cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences","volume":"87","author":"Stubbs","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/417182a","article-title":"Identification of a factor that links apoptotic cells to phagocytes","volume":"417","author":"Hanayama","year":"2002","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1091\/mbc.e05-02-0128","article-title":"Mfge8 is critical for mammary gland remodeling during involution","volume":"16","author":"Atabai","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1073\/pnas.0704756104","article-title":"Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis","volume":"104","author":"Nandrot","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1159\/000119861","article-title":"Lack of alphavbeta5 integrin receptor or its ligand MFG-E8: Distinct effects on retinal function","volume":"40","author":"Nandrot","year":"2008","journal-title":"Ophthal. Res."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Wang, P. (2014). MFG-E8: Origin, structure, expression, functions and regulation. MFG-E8 and Inflammation, Springer.","DOI":"10.1007\/978-94-017-8765-9"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/jcb.22076","article-title":"SED1\/MFG-E8: A bimotif protein that orchestrates diverse cellular interactions","volume":"106","author":"Raymond","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1095\/biolreprod58.4.1057","article-title":"Molecular cloning and characterization of P47, a novel boar sperm-associated zona pellucida-binding protein homologous to a family of mammalian secretory proteins","volume":"58","author":"Ensslin","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1242\/jcs.041731","article-title":"A novel role for SED1 (MFG-E8) in maintaining the integrity of the epididymal epithelium","volume":"122","author":"Raymond","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Li, D., Rongchun, W., Lu, W., and Ma, Y. (2024). Exploring the potential of MFG-E8 in neurodegenerative diseases. Crit Rev Food Sci Nutr, 1\u201315.","DOI":"10.1080\/10408398.2024.2417800"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1140\/epje\/s10189-023-00372-w","article-title":"MFG-E8: A model of multiple binding modes associated with ps-binding proteins","volume":"46","author":"Suwatthee","year":"2023","journal-title":"Eur. Phys. J. E"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.pep.2016.04.006","article-title":"Expression, purification, and characterization of recombinant human and murine milk fat globule-epidermal growth factor-factor 8","volume":"124","author":"Castellanos","year":"2016","journal-title":"Protein Expr. Purif."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"105720","DOI":"10.1016\/j.pep.2020.105720","article-title":"The structure and properties of MFG-E8 and the In vitro assessment of its toxic effects on myoblast cells","volume":"178","author":"Li","year":"2021","journal-title":"Protein Expr. Purif."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1073\/pnas.0610296104","article-title":"The EGF repeat and discoidin domain protein, SED1\/MFG-E8, is required for mammary gland branching morphogenesis","volume":"104","author":"Ensslin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.ijbiomac.2018.04.026","article-title":"Milk fat globule membrane protein promotes C(2)C(12) cell proliferation through the PI3K\/Akt signaling pathway","volume":"114","author":"Li","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cellimm.2018.05.008","article-title":"MFG-E8 inhibits A\u03b2-induced microglial production of cathelicidin-related antimicrobial peptide: A suitable target against Alzheimer\u2019s disease","volume":"331","author":"Xu","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41419-023-05607-4","article-title":"Schwann cell-derived exosomes containing MFG-E8 modify macrophage\/microglial polarization for attenuating inflammation via the SOCS3\/STAT3 pathway after spinal cord injury","volume":"14","author":"Ren","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1126\/science.285.5430.1028","article-title":"Integrin signaling","volume":"285","author":"Giancotti","year":"1999","journal-title":"Science"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.yexcr.2003.09.011","article-title":"The opsonin MFG-E8 is a ligand for the alphavbeta5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells","volume":"292","author":"Akakura","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Lee, J., Geum, D., Park, D.-H., and Kim, J.-H. (2024). Molecular targeting of ischemic stroke: The promise of na\u00efve and engineered extracellular vesicles. Pharmaceutics, 16.","DOI":"10.20944\/preprints202411.0189.v1"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1006\/bbrc.1999.1752","article-title":"Annexin V counteracts apoptosis while inducing Ca2+ influx in human lymphocytic T cells","volume":"265","author":"Solito","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/nsb1195-968","article-title":"Ca2+-bridging mechanism and phospholipid head group recognition in the membrane-binding protein annexin V","volume":"2","author":"Swairjo","year":"1995","journal-title":"Nat. Struct. Biol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bbamem.2004.09.006","article-title":"Lactadherin binds selectively to membranes containing phosphatidyl-L-serine and increased curvature","volume":"1667","author":"Shi","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.bbamem.2011.08.032","article-title":"Lactadherin binds to phosphatidylserine-containing vesicles in a two-step mechanism sensitive to vesicle size and composition","volume":"1818","author":"Otzen","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.bbamem.2012.12.009","article-title":"NMR solution structure of C2 domain of MFG-E8 and insights into its molecular recognition with phosphatidylserine","volume":"1828","author":"Ye","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1083\/jcb.201012028","article-title":"High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine","volume":"194","author":"Fairn","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1021\/bi963119m","article-title":"Bovine PAS-6\/7 binds alpha v beta 5 integrins and anionic phospholipids through two domains","volume":"36","author":"Andersen","year":"1997","journal-title":"Biochemistry"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000014020","article-title":"Glycoproteins of the human milk fat globule in the protection of the breast-fed infant against infections","volume":"74","author":"Peterson","year":"1998","journal-title":"Biol. Neonate"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"6200","DOI":"10.1021\/bi992221r","article-title":"Functional analyses of two cellular binding domains of bovine lactadherin","volume":"39","author":"Andersen","year":"2000","journal-title":"Biochemistry"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1046\/j.1432-1033.2002.02758.x","article-title":"Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles","volume":"269","author":"Oshima","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12974-020-02061-3","article-title":"Propofol suppresses microglial phagocytosis through the downregulation of MFG-E8","volume":"18","author":"Cai","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1172\/JCI1112","article-title":"Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine\/paracrine mechanisms involving TGF-beta, PGE2, and PAF","volume":"101","author":"Fadok","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"170","DOI":"10.2119\/molmed.2012.00260","article-title":"MFG-E8 and HMGB1 are involved in the mechanism underlying alcohol-induced impairment of macrophage efferocytosis","volume":"19","author":"Wang","year":"2013","journal-title":"Mol. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"9603271221093635","DOI":"10.1177\/09603271221093635","article-title":"MFGE8 decreased neuronal apoptosis and neuroinflammation to ameliorate early brain injury induced by subarachnoid hemorrhage through the inhibition of HMGB1","volume":"41","author":"Qiu","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Furuta, Y., Pena-Ramos, O., Li, Z., Chiao, L., and Zhou, Z. (2021). Calcium ions trigger the exposure of phosphatidylserine on the surface of necrotic cells. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009066"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.yexcr.2005.11.023","article-title":"Annexin A5 inhibits engulfment through internalization of PS-expressing cell membrane patches","volume":"312","author":"Kenis","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1083\/jcb.200903020","article-title":"Contribution of phosphatidylserine to membrane surface charge and protein targeting during phagosome maturation","volume":"185","author":"Yeung","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s11481-008-9118-2","article-title":"MFG-E8 regulates microglial phagocytosis of apoptotic neurons","volume":"3","author":"Fuller","year":"2008","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.freeradbiomed.2025.01.050","article-title":"hESC-derived extracellular vesicles enriched with MFGE-8 and the GSH redox system act as senotherapeutics for neural stem cells in ischemic stroke","volume":"229","author":"Lee","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1038\/s12276-023-01070-5","article-title":"After cell death: The molecular machinery of efferocytosis","volume":"55","author":"Moon","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"5983","DOI":"10.4049\/jimmunol.0802994","article-title":"Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected]","volume":"183","author":"Miksa","year":"2009","journal-title":"J. Immunol."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Wang, P. (2014). Autoimmune diseases and the role of MFG-E8. MFG-E8 and Inflammation, Springer.","DOI":"10.1007\/978-94-017-8765-9"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.20040342","article-title":"Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice","volume":"200","author":"Asano","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"270302","DOI":"10.1155\/2014\/270302","article-title":"Functional roles of Syk in macrophage-mediated inflammatory responses","volume":"2014","author":"Yi","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"979105","DOI":"10.1155\/2012\/979105","article-title":"The pivotal role of TBK1 in inflammatory responses mediated by macrophages","volume":"2012","author":"Yu","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41419-018-0437-9","article-title":"Kir6.1\/K-ATP channel modulates microglia phenotypes: Implication in Parkinson\u2019s disease","volume":"9","author":"Du","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Taylor, X., Cisternas, P., Jury, N., Martinez, P., Huang, X., You, Y., Redding-Ochoa, J., Vidal, R., Zhang, J., and Troncoso, J. (2022). Activated endothelial cells induce a distinct type of astrocytic reactivity. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03237-8"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.4103\/1673-5374.306064","article-title":"Astrocytes: A double-edged sword in neurodegenerative diseases","volume":"16","author":"Ding","year":"2021","journal-title":"Neural. Regen. Res."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Liu, L.R., Liu, J.C., Bao, J.S., Bai, Q.Q., and Wang, G.Q. (2020). Interaction of microglia and astrocytes in the neurovascular unit. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01024"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/cdd.2013.82","article-title":"Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids","volume":"20","author":"Lauber","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.gendis.2021.06.007","article-title":"Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases","volume":"9","author":"He","year":"2022","journal-title":"Genes Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1016\/j.ymthe.2017.09.009","article-title":"Epigenetic modification of microRNA-200b contributes to diabetic vasculopathy","volume":"25","author":"Singh","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2119\/2007-00019.Miksa","article-title":"Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages","volume":"13","author":"Miksa","year":"2007","journal-title":"Mol. Med."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.prp.2018.12.036","article-title":"MFG-E8 overexpression is associated with poor prognosis in breast cancer patients","volume":"215","author":"Yu","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1084\/jem.20082614","article-title":"Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms","volume":"206","author":"Jinushi","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1365-2133.2011.10409.x","article-title":"Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma","volume":"165","author":"Oba","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s40478-021-01257-9","article-title":"MFG-E8 (LACTADHERIN): A novel marker associated with cerebral amyloid angiopathy","volume":"9","author":"Marazuela","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1158\/0008-5472.CAN-15-2812","article-title":"MFG-E8 Drives Melanoma Growth by Stimulating Mesenchymal Stromal Cell-Induced Angiogenesis and M2 Polarization of Tumor-Associated Macrophages","volume":"76","author":"Yamada","year":"2016","journal-title":"Cancer Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1111\/cas.16099","article-title":"Potent CTLs can be induced against tumor cells in an environment of lower levels of systemic MFG-E8","volume":"115","author":"Mizote","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Shimagaki, T., Yoshio, S., Kawai, H., Sakamoto, Y., Doi, H., Matsuda, M., Mori, T., Osawa, Y., Fukai, M., and Yoshida, T. (2019). Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-52356-6"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1111\/1750-3841.70235","article-title":"MFG-E8 in Microglial Regulation: A Review of Basic Research in the Central Nervous System","volume":"90","author":"Li","year":"2025","journal-title":"J. Food Sci."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1182\/blood-2008-06-162404","article-title":"CX3CL1\/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis","volume":"112","author":"Truman","year":"2008","journal-title":"Blood"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2015.11.003","article-title":"Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders","volume":"103","author":"Jha","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Zhang, B., Wei, Y.Z., Wang, G.Q., Li, D.D., Shi, J.S., and Zhang, F. (2018). Targeting MAPK pathways by naringenin modulates microglia M1\/M2 polarization in lipopolysaccharide-stimulated cultures. Front. Cell Neurosci., 12.","DOI":"10.3389\/fncel.2018.00531"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrneurol.2014.207","article-title":"Microglial and macrophage polarization\u2014New prospects for brain repair","volume":"11","author":"Hu","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/path.4133","article-title":"Macrophage plasticity and polarization in tissue repair and remodelling","volume":"229","author":"Mantovani","year":"2013","journal-title":"J. Pathol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1126\/science.1094359","article-title":"Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice","volume":"304","author":"Hanayama","year":"2004","journal-title":"Science"},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Sokolova, D., Ghansah, S.A., Puletti, F., Georgiades, T., De Schepper, S., Zheng, Y., Crowley, G., Wu, L., Rueda-Carrasco, J., and Koutsiouroumpa, A. (2024). Astrocyte-derived MFG-E8 facilitates microglial synapse elimination in Alzheimer\u2019s disease mouse models. bioRxiv.","DOI":"10.1101\/2024.08.31.606944"},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Wang, E.Y., Chen, H.S., Wu, M.C., Yang, Y.L., Wang, H.L., Liu, C.W., and Lai, T.W. (2024). Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0308464"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/jcp.26918","article-title":"MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-\u03baB and PI3K-Akt pathways","volume":"234","author":"Xu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/jcb.25142","article-title":"Molecular mechanisms underlying the regulation of the MFG-E8 gene promoter activity in physiological and inflammatory conditions","volume":"116","author":"Wang","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Bu, H.F., Subramanian, S., Geng, H., Wang, X., Liu, F., Chou, P.M., Du, C., De Plaen, I.G., and Tan, X.D. (2021). MFG-E8 plays an important role in attenuating cerulein-induced acute pancreatitis in mice. Cells, 10.","DOI":"10.3390\/cells10040728"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1097\/CM9.0000000000003363","article-title":"Efferocytosis: A new therapeutic target for stroke","volume":"137","author":"Gao","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Lam, A.L., and Heit, B. (2021). Having an Old Friend for Dinner: The Interplay between Apoptotic Cells and Efferocytes. Cells, 10.","DOI":"10.20944\/preprints202104.0751.v1"},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Cheyuo, C., Aziz, M., Yang, W.L., Jacob, A., Zhou, M., and Wang, P. (2015). Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem cell proliferation and migration after cerebral ischemia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122833"},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Chaung, W., Ma, G., Jacob, A., Brenner, M., and Wang, P. (2023). Human cell-expressed tag-free rhMFG-E8 as an effective radiation mitigator. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-49499-y"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1111\/j.1476-5381.2012.01916.x","article-title":"The successes and limitations of preclinical studies in predicting the pharmacodynamics and safety of cell-surface-targeted biological agents in patients","volume":"166","author":"Polson","year":"2012","journal-title":"Br. J. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8708\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:23Z","timestamp":1760035283000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,6]]},"references-count":234,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178708"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178708","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,6]]}}}