Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood-brain barrier. Nat Med 19(12):1584–1596. https://doi.org/10.1038/nm.3407

Article  PubMed  PubMed Central  Google Scholar 

Nadareishvili Z, Simpkins AN, Hitomi E, Reyes D, Leigh R (2019) Post-stroke blood-brain barrier disruption and poor functional outcome in patients receiving thrombolytic therapy. Cerebrovasc Dis 47(3–4):135–142. https://doi.org/10.1159/000499666

Article  PubMed  Google Scholar 

Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14(3):133–150. https://doi.org/10.1038/nrneurol.2017.188

Article  PubMed  PubMed Central  Google Scholar 

Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2019) Blood-brain barrier: from physiology to disease and back. Physiol Rev 99(1):21–78. https://doi.org/10.1152/physrev.00050.2017

Article  PubMed  Google Scholar 

Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MVL, Chen J, Keep RF, Shi Y (2018) Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol 163:144–171. https://doi.org/10.1016/j.pneurobio.2017.10.001

Article  PubMed  Google Scholar 

Yang C, Hawkins KE, Dore S, Candelario-Jalil E (2019) Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. Am J Physiol Cell Physiol 316(2):C135–C153. https://doi.org/10.1152/ajpcell.00136.2018

Article  PubMed  Google Scholar 

Wang Y, Xiao G, He S, Liu X, Zhu L, Yang X, Zhang Y, Orgah J, Feng Y, Wang X, Zhang B, Zhu Y (2020) Protection against acute cerebral ischemia/reperfusion injury by QiShenYiQi via neuroinflammatory network mobilization. Biomed Pharmacother 125:109945. https://doi.org/10.1016/j.biopha.2020.109945

Article  PubMed  Google Scholar 

Bernardo-Castro S, Sousa JA, Bras A, Cecilia C, Rodrigues B, Almendra L, Machado C, Santo G, Silva F, Ferreira L, Santana I, Sargento-Freitas J (2020) Pathophysiology of blood-brain barrier permeability throughout the different stages of ischemic stroke and its implication on hemorrhagic transformation and recovery. Front Neurol 11:594672. https://doi.org/10.3389/fneur.2020.594672

Article  PubMed  PubMed Central  Google Scholar 

Xu M, Wu RX, Li XL, Zeng YS, Liang JY, Fu K, Liang Y, Wang Z (2022) Traditional medicine in China for ischemic stroke: bioactive components, pharmacology, and mechanisms. J Integr Neurosci 21(1):26. https://doi.org/10.31083/j.jin2101026

Article  PubMed  Google Scholar 

Su CY, Ming QL, Rahman K, Han T, Qin LP (2015) Salvia miltiorrhiza: traditional medicinal uses, chemistry, and pharmacology. Chin J Nat Med 13(3):163–182. https://doi.org/10.1016/S1875-5364(15)30002-9

Article  PubMed  Google Scholar 

Chen Z, Zhang C, Gao F, Fu Q, Fu C, He Y, Zhang J (2018) A systematic review on the rhizome of Ligusticum chuanxiong Hort. (Chuanxiong). Food Chem Toxicol 119:309–325. https://doi.org/10.1016/j.fct.2018.02.050

Article  PubMed  Google Scholar 

Yin C, Zhang M, Jin S, Zhou Y, Ding L, Lv Q, Huang Z, Zhou J, Chen J, Wang P, Zhang S, You Q (2024) Mechanism of Salvia miltiorrhiza Bunge extract to alleviate chronic sleep deprivation-induced cognitive dysfunction in rats. Phytomedicine 130:155725. https://doi.org/10.1016/j.phymed.2024.155725

Article  PubMed  Google Scholar 

Yu B, Yao Y, Zhang X, Ruan M, Zhang Z, Xu L, Liang T, Lu J (2021) Synergic neuroprotection between Ligusticum chuanxiong Hort and borneol against ischemic stroke by neurogenesis via modulating reactive astrogliosis and maintaining the blood-brain barrier. Front Pharmacol 12:666790. https://doi.org/10.3389/fphar.2021.666790

Article  PubMed  PubMed Central  Google Scholar 

Wang Y, Li Y, Zhou Y, Gao Y, Zhao L (2024) Guanxinning tablet alleviates post-ischemic stroke injury via regulating complement and coagulation cascades pathway and inflammatory network mobilization. Drug Des Devel Ther 18:4183–4202. https://doi.org/10.2147/DDDT.S479881

Article  PubMed  PubMed Central  Google Scholar 

Hui XR, Jin Q, He JM, Liu L, Zhao XP (2022) Mechanism of Guanxinning against cerebral ischemia-reperfusion injury in mice based on transcriptomic analysis. Zhongguo Zhong Yao Za Zhi 47(11):3015–3022. https://doi.org/10.19540/j.cnki.cjcmm.20220322.402

Article  PubMed  Google Scholar 

Xiao G, Lyu M, Li Z, Cao L, Liu X, Wang Y, He S, Chen Z, Du H, Feng Y, Wang J, Zhu Y (2021) Restoration of early deficiency of axonal guidance signaling by guanxinning injection as a novel therapeutic option for acute ischemic stroke. Pharmacol Res 165:105460. https://doi.org/10.1016/j.phrs.2021.105460

Article  PubMed  Google Scholar 

Biju TS, Priya VV, Francis AP (2023) Role of three-dimensional cell culture in therapeutics and diagnostics: an updated review. Drug Deliv Transl Res 13(9):2239–2253. https://doi.org/10.1007/s13346-023-01327-6

Article  PubMed  Google Scholar 

Urzì O, Gasparro R, Costanzo E, De Luca A, Giavaresi G, Fontana S, Alessandro R (2023) Three-dimensional cell cultures: the bridge between in vitro and in vivo models. Int J Mol Sci 24(15):12046. https://doi.org/10.3390/ijms241512046

Article  PubMed  PubMed Central  Google Scholar 

Duval K, Grover H, Han LH, Mou Y, Pegoraro AF, Fredberg J, Chen Z (2017) Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda) 32(4):266–277. https://doi.org/10.1152/physiol.00036.2016

Article  PubMed  Google Scholar 

Lee SY, Koo IS, Hwang HJ, Lee DW (2023) In vitro three-dimensional (3D) cell culture tools for spheroid and organoid models. SLAS Discov 28(4):119–137. https://doi.org/10.1016/j.slasd.2023.03.006

Article  PubMed  Google Scholar 

Perez-Lopez A, Torres-Suarez AI, Martin-Sabroso C, Aparicio-Blanco J (2023) An overview of in vitro 3D models of the blood-brain barrier as a tool to predict the in vivo permeability of nanomedicines. Adv Drug Deliv Rev 196:114816. https://doi.org/10.1016/j.addr.2023.114816

Article  PubMed  Google Scholar 

Fang Y, Eglen RM (2017) Three-dimensional cell cultures in drug discovery and development. SLAS Discov 22(5):456–472. https://doi.org/10.1177/1087057117696795

Article  PubMed  PubMed Central  Google Scholar 

Nzou G, Wicks RT, VanOstrand NR, Mekky GA, Seale SA, El-Taibany A, Wicks EE, Nechtman CM, Marrotte EJ, Makani VS, Murphy SV, Seeds MC, Jackson JD, Atala AJ (2020) Multicellular 3D neurovascular unit model for assessing hypoxia and neuroinflammation induced blood-brain barrier dysfunction. Sci Rep 10(1):9766. https://doi.org/10.1038/s41598-020-66487-8

Article  PubMed  PubMed Central  Google Scholar 

Urich E, Patsch C, Aigner S, Graf M, Iacone R, Freskgard PO (2013) Multicellular self-assembled spheroidal model of the blood brain barrier. Sci Rep 3:1500. https://doi.org/10.1038/srep01500

Article  PubMed  PubMed Central  Google Scholar 

Cho CF, Wolfe JM, Fadzen CM, Calligaris D, Hornburg K, Chiocca EA, Agar NYR, Pentelute BL, Lawler SE (2017) Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nat Commun 8:15623. https://doi.org/10.1038/ncomms15623

Article  PubMed  PubMed Central  Google Scholar 

Li Q, Sheng J, Baruscotti M, Liu Z, Wang Y, Zhao L (2025) Identification of Senkyunolide I as a novel modulator of hepatic steatosis and PPARα signaling in zebrafish and hamster models. J Ethnopharmacol 336:118743. https://doi.org/10.1016/j.jep.2024.118743

Article  PubMed  Google Scholar 

Du HY, Xue ZF, Xia ZT, He S, Yang J, Zhu Y (2022) Construction of 3D blood-brain barrier organoid oxygen-glucose deprivation model and exploration of the protective effect of Guanxinning injection. Acta Pharmaceutica Sinica 57(10):3086–3094. https://doi.org/10.16438/j.0513-4870.2021-1871

Article  Google Scholar 

Ko E, Poon MLS, Park E, Cho Y, Shin JH (2021) Engineering 3D cortical spheroids for an in vitro ischemic stroke model. ACS Biomater Sci Eng 7(8):3845–3860. https://doi.org/10.1021/acsbiomaterials.1c00406

Article  PubMed  Google Scholar 

Kitamura K, Umehara K, Ito R, Yamaura Y, Komori T, Morio H, Akita H, Furihata T (2021) Development, characterization and potential applications of a multicellular spheroidal human blood-brain barrier model integrating three conditionally immortalized cell lines. Biol Pharm Bull 44(7):984–991. https://doi.org/10.1248/bpb.b21-00218

Article  PubMed