Feigin VL, Brainin M, Norrving B, Martins S, Sacco RL, Hacke W, et al. World Stroke Organization (WSO): global stroke fact sheet 2022. Int J Stroke. 2022;17:18–29.

Article  PubMed  Google Scholar 

Disorders NIoN, Group Sr-PSS. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–8.

Article  Google Scholar 

Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24h after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378:11–21.

Article  PubMed  Google Scholar 

Krishnan R, Mays W, Elijovich L. Complications of mechanical thrombectomy in acute ischemic stroke. Neurology. 2021;97:S115–S25.

Article  PubMed  Google Scholar 

Han W, Song Y, Rocha M, Shi Y. Ischemic brain edema: Emerging cellular mechanisms and therapeutic approaches. Neurobiol Dis. 2023;178:106029.

Turner RJ, Sharp FR. Implications of MMP9 for blood brain barrier disruption and hemorrhagic transformation following ischemic stroke. Front Cell Neurosci. 2016;10:56.

Article  PubMed  PubMed Central  Google Scholar 

Abdullahi W, Tripathi D, Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection. Am J Physiol Cell Physiol. 2018;315:C343–C56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burek M, König A, Lang M, Fiedler J, Oerter S, Roewer N, et al. Hypoxia-induced microRNA-212/132 alter blood-brain barrier integrity through inhibition of tight junction-associated proteins in human and mouse brain microvascular endothelial cells. Transl Stroke Res. 2019;10:672–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kang R, Gamdzyk M, Lenahan C, Tang J, Tan S, Zhang JH. The dual role of microglia in blood-brain barrier dysfunction after stroke. Curr Neuropharmacol. 2020;18:1237–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li X, Zhang Y, Chang J, Zhang C, Li L, Dai Y, et al. Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood-brain barrier in mfat-1 transgenic mice. Cell Mol Life Sci. 2023;80:71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarvari S, Moakedi F, Hone E, Simpkins JW, Ren X. Mechanisms in blood-brain barrier opening and metabolism-challenged cerebrovascular ischemia with emphasis on ischemic stroke. Metab Brain Dis. 2020;35:851–68.

Article  PubMed  PubMed Central  Google Scholar 

Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia. 2013;61:1939–58.

Article  PubMed  PubMed Central  Google Scholar 

Lana D, Ugolini F, Melani A, Nosi D, Pedata F, Giovannini MG. The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: protective effect of dipyridamole. Exp Gerontol. 2017;96:46–62.

Article  CAS  PubMed  Google Scholar 

Lyden PD, Lamb J, Kothari S, Toossi S, Boitano P, Rajput PS. Differential effects of hypothermia on neurovascular unit determine protective or toxic results: toward optimized therapeutic hypothermia. J Cereb Blood Flow Metab. 2019;39:1693–709.

Article  CAS  PubMed  Google Scholar 

Cheng J, Wang W, Xia Y, Li Y, Jia J, Xiao G. Regulators of phagocytosis as pharmacologic targets for stroke treatment. Front Pharmacol. 2023;14:1122527.

Zhang X, Song L, Li L, Zhu B, Huo L, Hu Z, et al. Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy. Signal Transduct Target Ther. 2021;6:235.

Bouter A, Carmeille R, Gounou C, Bouvet F, Degrelle S, Evain-Brion D, et al. Annexin-A5 and cell membrane repair. Placenta. 2015;36:S43–S9.

Article  CAS  PubMed  Google Scholar 

Schutters K, Reutelingsperger C. Phosphatidylserine targeting for diagnosis and treatment of human diseases. Apoptosis. 2010;15:1072–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kang TH, Park JH, Yang A, Park HJ, Lee SE, Kim YS, et al. Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment. Nat Commun. 2020;11:1137.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rand ML, Wang H, Pluthero FG, Stafford AR, Ni R, Vaezzadeh N, et al. J Diannexin, an annexin A5 homodimer, binds phosphatidylserine with high affinity and is a potent inhibitor of platelet-mediated events during thrombus formation. J Thromb Haemost. 2012;10:1109–19.

Article  CAS  PubMed  Google Scholar 

Zhou T, Li Y, Li X, Zeng F, Rao Y, He Y, et al. Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice. Nat Commun. 2022;13:6233.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu C, Jiang Q, Hu M, Tan C, Ji Y, Yu H, et al. Preliminary biological evaluation of novel 99mTc-Cys-Annexin A5 as a apoptosis imaging agent. Molecules. 2013;18:6908–18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang J, He L, Chen D, Pi Y, Zhou W, Xiong X, et al. Quantitative analysis of annexin V-membrane interaction by flow cytometry. Eur Biophys J. 2015;44:325–36.

Article  CAS  PubMed  Google Scholar 

Zhang M, Wu X, Xu Y, He M, Yang J, Li J, et al. The cystathionine β-synthase/hydrogen sulfide pathway contributes to microglia-mediated neuroinflammation following cerebral ischemia. Brain Behav Immun. 2017;66:332–46.

Wang Y, Jia J, Ao G, Hu L, Liu H, Xiao Y, et al. Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia. J Neurochem. 2014;129:827–38.

Article  CAS  PubMed  Google Scholar 

Yan X, He M, Huang H, Wang Q, Hu Y, Wang X, et al. Endogenous H2S targets mitochondria to promote continual phagocytosis of erythrocytes by microglia after intracerebral hemorrhage. Redox Biol. 2022;56:102442.

Morizawa YM, Hirayama Y, Ohno N, Shibata S, Shigetomi E, Sui Y, et al. Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. Nat Commun. 2017;8:28.

Goldmann T, Wieghofer P, Müller PF, Wolf Y, Varol D, Yona S, et al. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci. 2013;16:1618–26.

Article  CAS  PubMed  Google Scholar 

Ambort D, Johansson MEV, Gustafsson JK, Nilsson HE, Ermund A, Johansson BR, et al. Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc Natl Acad Sci USA. 2012;109:5645–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang W. Protein aggregation and its inhibition in biopharmaceutics. Int J Pharm. 2005;289:1–30.

Article  CAS  PubMed  Google Scholar 

Lauritzen SP, Boye TL, Nylandsted J. Annexins are instrumental for efficient plasma membrane repair in cancer cells. Semin Cell Dev Biol. 2015;45:32–8.

Article  CAS  PubMed  Google Scholar 

Mamtilahun M, Tang G, Zhang Z, Wang Y, Tang Y, Yang G-Y. Targeting water in the brain: role of aquaporin-4 in ischemic brain edema. Curr Drug Targets. 2019;20:748–55.

Article  CAS  PubMed  Google Scholar 

Stokum JA, Mehta RI, Ivanova S, Yu E, Gerzanich V, Simard JM. Heterogeneity of aquaporin-4 localization and expression after focal cerebral ischemia underlies differences in white versus grey matter swelling. Acta Neuropathol Commun. 2015;3:61.

Schlegel R, Williamson P. Phosphatidylserine, a death knell. Cell Death Differ. 2001;8:551–63.

Article  CAS  PubMed  Google Scholar 

Segawa K, Nagata S. An apoptotic ‘eat me’signal: phosphatidylserine exposure. Trends Cell Biol. 2015;25:639–50.

Article  CAS  PubMed  Google Scholar 

Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MV, Chen J, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol. 2018;163:144–71.

Article  PubMed  Google Scholar 

Prakash R, Carmichael ST. Blood-brain barrier breakdown and neovascularization processes after stroke and trau