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Review Article

Research progress of mechanisms for tight junction damage on blood–brain barrier inflammation

, , , , , & ORCID Icon show all
Pages 1579-1590 | Received 12 Mar 2020, Accepted 15 Jun 2020, Published online: 01 Jul 2020

References

  • Abbott, N.J., et al., 2010. Structure and function of the blood–brain barrier. Neurobiology of disease, 37 (1), 13–25.
  • Abdul-Muneer, P.M., et al., 2015. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Molecular neurobiology, 51 (3), 966–979.
  • Akira, S., et al., 2001. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature immunology, 2 (8), 675–680.
  • Ao, L-y., et al., 2018. Immune cells after ischemic stroke onset: roles, migration, and target intervention. Journal of molecular neuroscience: Mn, 66 (3), 342–355.
  • Ayala-Torres, C. and Krug, S.M., 2019. Tricellulin effect on paracellular water transport. International journal of molecular sciences, 20 (22), E5700.
  • Bae, M.J., et al., 2016. Inhibition of MMP-2 and MMP-9 activities by Limonium tetragonum extract. Preventive nutrition and food science, 21 (1), 38–43.
  • Barkalow, F.J., et al., 1996. Brain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion. Blood, 88 (12), 4585–4593.
  • Bazzoni, G. and Dejana, E., 2004. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiological reviews, 84 (3), 869–901.
  • Beck, S.C., et al., 2019. Biomarkers in human anaphylaxis: a critical appraisal of current evidence and perspectives. Frontiers in immunology, 10, 494.
  • Bhowmick, S., et al., 2019. Impairment of pericyte-endothelium crosstalk leads to blood–brain barrier dysfunction following traumatic brain injury. Experimental neurology, 317, 260–270.
  • Borroni, E.M., et al., 2018. Chemokines sound the alarmin: the role of atypical chemokine in inflammation and cancer. Seminars in immunology, 38, 63–71.
  • Chaturvedi, M. and Kaczmarek, L., 2014. Mmp-9 inhibition: a therapeutic strategy in ischemic stroke. Molecular neurobiology, 49 (1), 563–573.
  • Chen, F., et al., 2018. Activation of EphA4 induced by EphrinA1 exacerbates disruption of the blood–brain barrier following cerebral ischemia-reperfusion via the Rho/ROCK signaling pathway. Experimental and therapeutic medicine, 16 (3), 2651–2658.
  • Chen, S., et al., 2018. Early abrogation of gelatinase activity extends the time window for tPA thrombolysis after embolic focal cerebral ischemia in mice. ENEURO, 5 (3), ENEURO.0391-17.2018.
  • Cherry, J.D., et al., 2014. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. Journal of neuroinflammation, 11, 98.
  • Chhor, V., et al., 2013. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain, behavior, and immunity, 32, 70–85.
  • Clausen, F., et al., 2011. Neutralization of interleukin-1beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice. European journal of neuroscience, 34 (1), 110–123.
  • Cording, J., et al., 2013. In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization. Journal of cell science, 126 (Pt 2), 554–564.
  • Cording, J., et al., 2015. Redox regulation of cell contacts by tricellulin and occludin: redox-sensitive cysteine sites in tricellulin regulate both tri- and bicellular junctions in tissue barriers as shown in hypoxia and ischemia. Antioxidants & redox signaling, 23 (13), 1035–1049.
  • Cording, J., et al., 2017. Trictide, a tricellulin-derived peptide to overcome cellular barriers. Annals of the New York academy of sciences, 1405 (1), 89–101.
  • Cunningham, K.E. and Turner, J.R., 2012. Myosin light chain kinase: pulling the strings of epithelial tight junction function. Annals of the New York academy of sciences, 1258, 34–42.
  • de Groot, B.L. and Grubmuller, H., 2001. Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science (New York, NY), 294 (5550), 2353–2357.
  • Deguine, J. and Barton, G.M., 2014. MyD88: a central player in innate immune signaling. F1000prime reports, 6, 97.
  • Dong, T., et al., 2018. The protective roles of L-borneolum, D-borneolum and synthetic borneol in cerebral ischaemia via modulation of the neurovascular unit. Biomedicine & pharmacotherapy = Pharmacotherapy, 102, 874–883.
  • Esmaeilzadeh, E., et al., 2019. Curcumin ameliorates experimental autoimmune encephalomyelitis in a C57BL/6 mouse model. Drug development research, 80 (5), 629–636.  
  • Eum, S.Y., et al., 2014. Disruption of epithelial barrier by quorum-sensing N-3-(oxododecanoyl)-homoserine lactone is mediated by matrix metalloproteinases. American journal of physiology-Gastrointestinal and liver physiology, 306 (11), G992–G1001.
  • Feng, S., et al., 2018. RhoA/ROCK-2 pathway inhibition and tight junction protein upregulation by catalpol suppresses lipopolysaccaride-induced disruption of blood–brain barrier permeability. Molecules, 23 (9). doi:10.3390/molecules23092371
  • Findley, M.K. and Koval, M., 2009. Regulation and roles for claudin-family tight junction proteins. IUBMB life, 61 (4), 431–437.
  • Geering, B., et al., 2013. Living and dying for inflammation: neutrophils, eosinophils, basophils. Trends in immunology, 34 (8), 398–409.
  • Gelderblom, M., et al., 2009. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke, 40 (5), 1849–1857.
  • Girolamo, F., et al., 2019. Defining the role of NG2-expressing cells in experimental models of multiple sclerosis. A biofunctional analysis of the neurovascular unit in wild type and NG2 null mice. PLoS one, 14 (3), e0213508.
  • Gonzalez-Mariscal, L., et al., 2000. Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules. Kidney international, 57 (6), 2386–2402.
  • Greene, C. and Campbell, M., 2016. Tight junction modulation of the blood brain barrier: CNS delivery of small molecules. Tissue barriers, 4 (1), e1138017.
  • Gupta, S.C., et al., 2018. Inflammation, a double-edge sword for cancer and other age-related diseases. Frontiers in immunology, 9, 2160.
  • Hasegawa, M. and Takehara, K., 2012. Potential immunologic targets for treating fibrosis in systemic sclerosis: a review focused on leukocytes and cytokines. Seminars in arthritis and rheumatism, 42 (3), 281–296.
  • Higashi, T. and Miller, A.L., 2017. Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells. Molecular biology of the cell, 28 (15), 2023–2034.
  • Hu, S., et al., 2019. Panax notoginseng saponins suppress lipopolysaccharide-induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF-κB inflammatory pathways. Phytotherapy research, 33 (12), 3163–3176.
  • Ikenouchi, J., et al., 2005. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. The journal of cell biology, 171 (6), 939–945.
  • Jickling, G.C., et al., 2015. Targeting neutrophils in ischemic stroke: translational insights from experimental studies. Journal of cerebral blood flow and metabolism: official journal of the international society of cerebral blood flow and metabolism, 35 (6), 888–901.
  • Karshovska, E., et al., 2015. Hyperreactivity of junctional adhesion molecule A-deficient platelets accelerates atherosclerosis in hyperlipidemic mice. Circulation research, 116 (4), 587–599.
  • Kaur, C. and Ling, E.A., 2008. Blood brain barrier in hypoxic-ischemic conditions. Current neurovascular research, 5 (1), 71–81.
  • Kim, E. and Cho, S., 2016. Microglia and monocyte-derived macrophages in stroke. Neurotherapeutics: the journal of the American society for experimental neurotherapeutics, 13 (4), 702–718.
  • Kim, J.H., et al., 2016a. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood–brain barrier permeability and altering tight junction/adhesion molecules. Comparative immunology, microbiology and infectious diseases, 48, 22–32.
  • Kim, J.Y., et al., 2016b. Inflammation after ischemic stroke: the role of leukocytes and glial cells. Experimental neurobiology, 25 (5), 241–251.
  • Kojima, T., et al., 2010. c-Jun N-terminal kinase is largely involved in the regulation of tricellular tight junctions via tricellulin in human pancreatic duct epithelial cells. Journal of cellular physiology, 225 (3), 720–733.
  • Krause, G., et al., 2008. Structure and function of claudins. Biochimica et biophysica acta, 1778 (3), 631–645.
  • Krug, S.M., et al., 2009. Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Molecular biology of the cell, 20 (16), 3713–3724.
  • Krug, S.M., et al., 2017. Angubindin-1, a novel paracellular absorption enhancer acting at the tricellular tight junction. Journal of controlled release: official journal of the controlled release society, 260, 1–11.
  • Krug, S.M., et al., 2018. Tricellulin is regulated via interleukin-13-receptor α2, affects macromolecule uptake, and is decreased in ulcerative colitis. Mucosal immunology, 11 (2), 345–356.
  • Li, Z., et al., 2018. Naringin attenuates MLC phosphorylation and NF-κB activation to protect sepsis-induced intestinal injury via RhoA/ROCK pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 103, 50–58.
  • Lin, R., et al., 2018. Interleukin-10 attenuates impairment of the blood–brain barrier in a severe acute pancreatitis rat model. Journal of inflammation (London, England), 15, 4.
  • Liu, J., et al., 2012a. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood–brain barrier damage in early ischemic stroke stage. The journal of neuroscience: the official journal of the Society for neuroscience, 32 (9), 3044–3057.
  • Liu, W.Y., et al., 2012b. Tight junction in blood–brain barrier: an overview of structure, regulation, and regulator substances. CNS neuroscience & therapeutics, 18 (8), 609–615.
  • Llevenes, P., et al., 2018. Thyroid hormones affect nitrergic innervation function in rat mesenteric artery: role of the PI3K/AKT pathway vascular pharmacology. Vascular pharmacology, 108, 36–45.
  • Lv, J., et al., 2018. Focusing on claudin-5: a promising candidate in the regulation of BBB to treat ischemic stroke. Progress in neurobiology, 161, 79–96.
  • Lv, Y., et al., 2019. Myosin IIA regulated tight junction in oxygen glucose-deprived brain endothelial cells via activation of TLR4/PI3K/Akt/JNK1/2/14-3-3ε/NF-κB/MMP9 signal transduction pathway. Cellular and molecular neurobiology, 39 (2), 301–319.
  • Mackenzie, F. and Ruhrberg, C., 2012. Diverse roles for VEGF-A in the nervous system. Development (Cambridge, England), 139 (8), 1371–1380.
  • Mao, B.P., et al., 2019. CAMSAP2 is a microtubule minus-end targeting protein that regulates BTB dynamics through cytoskeletal organization. Endocrinology, 160 (6), 1448–1467.
  • Mariano, C., et al., 2011a. A look at tricellulin and its role in tight junction formation and maintenance. European journal of cell biology, 90 (10), 787–796.
  • Mariano, C., et al., 2011b. Evidence of tricellulin expression by immune cells, particularly microglia. Biochemical and biophysical research communications, 409 (4), 799–802.
  • Matsubara, A., et al., 2018. Tricellulin expression and its deletion effects in the endolymphatic sac. The journal of international advanced otology, 14 (2), 312–316.
  • Mesli, S., et al., 2004. Distribution of the lipolysis stimulated receptor in adult and embryonic murine tissues and lethality of LSR−/− embryos at 12.5 to 14.5 days of gestation. European journal of biochemistry, 271 (15), 3103–3114.
  • Modarres, H.P., et al., 2018. In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain. Journal of controlled release: official journal of the controlled release society, 273, 108–130.
  • Nagyoszi, P., et al., 2010. Expression and regulation of toll-like receptors in cerebral endothelial cells. Neurochemistry international, 57 (5), 556–564.
  • Nayak, G., et al., 2013. Tricellulin deficiency affects tight junction architecture and cochlear hair cells. The journal of clinical investigation, 123 (9), 4036–4049.
  • Nitta, T., et al., 2003. Size-selective loosening of the blood–brain barrier in claudin-5-deficient mice. Journal of cell biology, 161 (3), 653–660.
  • Nusrat, A., et al., 2005. Multiple protein interactions involving proposed extracellular loop domains of the tight junction protein occludin. Molecular biology of the cell, 16 (4), 1725–1734.
  • Patel, A.R., et al., 2013. Microglia and ischemic stroke: a double-edged sword International journal of physiology. International journal of physiology, pathophysiology and pharmacology, 5 (2), 73–90.
  • Peddibhotla, S.S., et al., 2013. Tetraspanin CD9 links junctional adhesion molecule-A to αvβ3 integrin to mediate basic fibroblast growth factor-specific angiogenic signaling. Molecular biology of the cell, 24 (7), 933–944.
  • Piontek, J., et al., 2011. Elucidating the principles of the molecular organization of heteropolymeric tight junction strands. Cellular and molecular life sciences, 68 (23), 3903–3918.
  • Rachakonda, G., et al., 2016. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer. Cellular signalling, 28 (10), 1537–1544.
  • Ranieri, R., et al., 2016. Cannabinoids and neuro-inflammation: regulation of brain immune response. Recent patents on CNS drug discovery, 10 (2), 178–203.
  • Ransohoff, R.M. and Brown, M.A., 2012. Innate immunity in the central nervous system. The journal of clinical investigation, 122 (4), 1164–1171.
  • Reinhard, S.M., et al., 2015. A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders. Frontiers in cellular neuroscience, 9, 280.
  • Rigor, R.R., et al., 2013. Myosin light chain kinase signaling in endothelial barrier dysfunction. Medicinal research reviews, 33 (5), 911–933.
  • Saitou, M., et al., 2000. Complex phenotype of mice lacking occludin, a component of tight junction strands. Molecular biology of the cell, 11 (12), 4131–4142.
  • Sanz, M.J. and Kubes, P., 2012. Neutrophil-active chemokines in in vivo imaging of neutrophil trafficking. European journal of immunology, 42 (2), 278–283.
  • Sela, U., et al., 2018. Strains of bacterial species induce a greatly varied acute adaptive immune response: the contribution of the accessory genome. PLoS pathogens, 14 (1), e1006726.
  • Shi, H., et al., 2018. Chemokine (C-X-C motif) ligand 1 and CXCL2 produced by tumor promote the generation of monocytic myeloid-derived suppressor cells. Cancer science, 109 (12), 3826–3839.
  • Shigemoto-Mogami, Y., et al., 2018. Activated microglia disrupt the blood–brain barrier and induce chemokines and cytokines in a rat in vitro model. Frontiers in cellular neuroscience, 12, 494.
  • Shin, K. and Margolis, B., 2006. ZOning out tight junctions. Cell, 126 (4), 647–649.
  • Smolders, J., et al., 2018. Tissue-resident memory T cells populate the human brain. Nature communications, 9 (1), 4593.
  • Smyth, L.C.D., et al., 2018. Unique and shared inflammatory profiles of human brain endothelia and pericytes. Journal of neuroinflammation, 15 (1), 138.
  • Sohet, F., et al., 2015. LSR/angulin-1 is a tricellular tight junction protein involved in blood–brain barrier formation. The journal of cell biology, 208 (6), 703–711.
  • Song, X., et al., 2018. Receptor mediated transcytosis in biological barrier: the influence of receptor character and their ligand density on the transmembrane pathway of active-targeting nanocarriers. Biomaterials, 180, 78–90.
  • Spadaro, D., et al., 2014. ZO proteins redundantly regulate the transcription factor DbpA/ZONAB. The journal of biological chemistry, 289 (32), 22500–22511.
  • Staehelin, L.A., et al., 1969. Freeze-etch appearance of the tight junctions in the epithelium of small and large intestine of mice. Protoplasma, 67 (2), 165–184.
  • Staehelin, L.A., 1973. Further observations on the fine structure of freeze-cleaved tight junctions. Journal of cell science, 13 (3), 763–786.
  • Stamatovic, S.M., et al., 2016. Junctional proteins of the blood–brain barrier: new insights into function and dysfunction. Tissue barriers, 4 (1), e1154641.
  • Straub, R.H., 2017. The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nature reviews Rheumatology, 13 (12), 743–751.
  • Subhramanyam, C.S., et al., 2019. Microglia-mediated neuroinflammation in neurodegenerative diseases. Seminars in cell & developmental biology, 94, 112–120.
  • Sun, N., et al., 2016. Ghrelin attenuates brain injury in septic mice via PI3K/Akt signaling activation. Brain research bulletin, 124, 278–285.
  • Sun, Z.Y., et al., 2019. Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion. Neural regeneration research, 14 (5), 783–793.
  • Tan, S., et al., 2019. Neutralization of interleukin-9 ameliorates experimental stroke by repairing the blood–brain barrier via down-regulation of astrocyte-derived vascular endothelial growth factor. A FASEB journal: official publication of the Federation of. FASEB journal: official publication of the federation of American societies for experimental biology, 33 (3), 4376–4387.
  • Tao, X.G., et al., 2017. Protective effects of calpain inhibition on neurovascular unit injury through downregulating nuclear factor-kappaB-related inflammation during traumatic brain injury in mice. Chinese medical journal, 130 (2), 187–198.
  • Tietz, S. and Engelhardt, B., 2015. Brain barriers: crosstalk between complex tight junctions and adherens junctions. The journal of cell biology, 209 (4), 493–506.
  • Tornavaca, O., et al., 2015. ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. The journal of cell biology, 208 (6), 821–838.
  • Trivedi, P.J. and Adams, D.H., 2018. Chemokines and chemokine receptors as therapeutic targets in inflammatory bowel disease; pitfalls and promise. Journal of Crohn's & Colitis, 12 (suppl_2), S641–S652.
  • Tsukita, S., et al., 2001. Multifunctional strands in tight junctions. Nature reviews. Molecular cell biology, 2 (4), 285–293.
  • Umeda, K., et al., 2006. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell, 126 (4), 741–754.
  • Van Dyken, P. and Lacoste, B., 2018. Impact of metabolic syndrome on neuroinflammation and the blood–brain barrier. Frontiers in neuroscience, 12, 930.
  • Van Itallie, C.M. and Anderson, J.M., 2018. Phosphorylation of tight junction transmembrane proteins: many sites, much to do. Tissue barriers, 6 (1), e1382671.
  • Varnum, M.M. and Ikezu, T., 2012. The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain. Archivum immunologiae et therapiae experimentalis (Warsz.), 60 (4), 251–266.
  • Wang, H., et al., 2019. Dynamic effects of ioversol on the permeability of the blood–brain barrier and the expression of ZO-1/occludin in rats. Journal of molecular neuroscience, 68 (2), 295–303.
  • Wang, P.F., et al., 2015. Function and mechanism of toll-like receptors in cerebral ischemic tolerance: from preconditioning to treatment. Journal of neuroinflammation, 12, 80.
  • Wang, T.H., et al., 2017. LPS pretreatment provides neuroprotective roles in rats with subarachnoid hemorrhage by downregulating MMP9 and caspase3 associated with TLR4 signaling activation. Molecular neurobiology, 54 (10), 7746–7760.
  • Wang, Y. and Lui, W.Y., 2012. Transforming growth factor-β1 attenuates junctional adhesion molecule-A and contributes to breast cancer cell invasion. European journal of cancer, 48 (18), 3475–3487.
  • Wen, J., et al., 2014. Overexpression of netrin-1 increases the expression of tight junction-associated proteins, claudin-5, occludin, and ZO-1, following traumatic brain injury in rats. Experimental and therapeutic medicine, 8 (3), 881–886.
  • Williams, D.W., et al., 2015. JAM-A and ALCAM are therapeutic targets to inhibit diapedesis across the BBB of CD14 + CD16+ monocytes in HIV-infected individuals. Journal of leukocyte biology, 97 (2), 401–412.
  • Willott, E., et al., 1992. Localization and differential expression of two isoforms of the tight junction protein ZO-1. The American journal of physiology, 262 (5 Pt 1), C1119–C1124.
  • Won, S., et al., 2014. Progesterone attenuates hemorrhagic transformation after delayed tPA treatment in an experimental model of stroke in rats: involvement of the VEGF-MMP pathway. Journal of cerebral blood flow and metabolism: official journal of the international society of cerebral blood flow and metabolism, 34 (1), 72–80.
  • Wu, H., et al., 2010. Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema. Neurochemistry international, 57 (3), 248–253.
  • WY, L., et al., 2012. Tight junction in blood–brain barrier: an overview of structure, regulation, and regulator substances. CNS neuroscience & therapeutics, 18 (8), 609–615.
  • Yang, X., et al., 2016. Treatment with tanshinone IIA suppresses disruption of the blood–brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis. European journal of pharmacology, 771, 18–28.
  • Yang, X., et al., 2017. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury. Brain, behavior, and immunity, 64, 162–172.
  • Yang, Y., et al., 2007. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. Journal of cerebral blood flow and metabolism: official journal of the international society of cerebral blood flow and metabolism, 27 (4), 697–709.
  • Yang, Y. and Rosenberg, G.A., 2011. Blood–brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke, 42 (11), 3323–3328.
  • Yu, W.B., et al., 2019. The therapeutic potential of ginkgolide K in experimental autoimmune encephalomyelitis via peripheral immunomodulation. International immunopharmacology, 70, 284–294.
  • Zhai, L., et al., 2017. Picroside II protects the blood–brain barrier by inhibiting the oxidative signaling pathway in cerebral ischemia-reperfusion injury. PLoS one, 12 (4), e0174414.
  • Zhang, D., et al., 2017. Metformin ameliorates BSCB disruption by inhibiting neutrophil infiltration and MMP-9 expression but not direct TJ proteins expression regulation. Journal of cellular and molecular medicine, 21 (12), 3322–3336.
  • Zhang, L., et al., 2018. The role of tight junction proteins in ovarian follicular development and ovarian cancer. Reproduction (Cambridge, England), 155 (4), *R183–r198.
  • Zheng, X., et al., 2018. Different concentrations of lipopolysaccharide regulate barrier function through the PI3K/Akt signalling pathway in human pulmonary microvascular endothelial cells. Scientific reports, 8 (1), 9963.
  • Zhu, H., et al., 2018. TLR2 ligand Pam3CSK4 regulates MMP-2/9 expression by MAPK/NF-κB signaling pathways in primary brain microvascular endothelial cells. Neurochemical research, 43 (10), 1897–1904.
  • Zhu, H., et al., 2019. MMP-9 upregulation is attenuated by the monoclonal TLR2 antagonist T2.5 after oxygen-glucose deprivation and reoxygenation in rat brain microvascular endothelial cells. Journal of stroke and cerebrovascular diseases: the official journal of national stroke association, 28 (1), 97–106.

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