Intravenous immunoglobulin (IVIg) provides protection against endothelial cell dysfunction and death in ischemic stroke

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• 作者：Alexander Widiapradja (1) (2)
  Tomislav Santro (2)
  Milan Basta (3)
  Christopher G Sobey (4)
  Silvia Manzanero (2) (5)
  Thiruma V Arumugam (1) (2)
  
  1. Department of Physiology ; Yong Loo Lin School of Medicine ; National University of Singapore ; Singapore ; 117597 ; Singapore
  2. School of Biomedical Sciences ; The University of Queensland ; St Lucia ; QLD ; 4072 ; Australia
  3. Biovisions ; Inc ; Potomac ; MD ; USA
  4. Department of Pharmacology ; Monash University ; Clayton ; Victoria ; Australia
  5. Australian Institute for Bioengineering & Nanotechnology ; The University of Queensland ; St Lucia ; QLD ; 4072 ; Australia
  
• 关键词：Intravenous immunoglobulin ; Ischemic stroke ; Blood鈥揵rain barrier ; Endothelium ; Permeability
• 刊名：Experimental & Translational Stroke Medicine
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：6
• 期：1
• 全文大小：737 KB
• 参考文献：1. McCormack, PL (2013) Immune globulin (human) 10% liquid: a review of its use in primary immunodeficiency disorders. BioDrugs 27: pp. 393-400 CrossRef
  2. Arumugam, TV, Tang, SC, Lathia, JD, Cheng, A, Mughal, MR, Chigurupati, S, Magnus, T, Chan, SL, Jo, DG, Ouyang, X, Fairlie, DP, Granger, DN, Vortmeyer, A, Basta, M, Mattson, MP (2007) Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc Natl Acad Sci U S A 104: pp. 14104-14109 CrossRef
  3. Widiapradja, A, Vegh, V, Lok, KZ, Manzanero, S, Thundyil, J, Gelderblom, M, Cheng, YL, Pavlovski, D, Tang, SC, Jo, DG, Magnus, T, Chan, SL, Sobey, CG, Reutens, D, Basta, M, Mattson, MP, Arumugam, TV (2012) Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways. J Neurochem 122: pp. 321-332 CrossRef
  4. Fann, DY, Lee, SY, Manzanero, S, Tang, SC, Gelderblom, M, Chunduri, P, Bernreuther, C, Glatzel, M, Cheng, YL, Thundyil, J, Widiapradja, A, Lok, KZ, Foo, SL, Wang, YC, Li, YI, Drummond, GR, Basta, M, Magnus, T, Jo, DG, Mattson, MP, Sobey, CG, Arumugam, TV (2013) Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 4: pp. e790 CrossRef
  5. Gelderblom, M, Leypoldt, F, Steinbach, K, Behrens, D, Choe, CU, Siler, DA, Arumugam, TV, Orthey, E, Gerloff, C, Tolosa, E, Magnus, T (2009) Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke 40: pp. 1849-1857 CrossRef
  6. Issekutz, AC, Rowter, D, Macmillan, HF (2011) Intravenous immunoglobulin G (IVIG) inhibits IL-1- and TNF-伪-dependent, but not chemotactic-factor-stimulated, neutrophil transendothelial migration. Clin Immunol 141: pp. 187-196 CrossRef
  7. Jang, JE, Hidalgo, A, Frenette, PS (2012) Intravenous immunoglobulins modulate neutrophil activation and vascular injury through Fc纬RIII and SHP-1. Circ Res 110: pp. 1057-1066 CrossRef
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  9. Sandoval, KE, Witt, KA (2008) Blood鈥揵rain barrier tight junction permeability and ischemic stroke. Neurobiol Dis 32: pp. 200-219 CrossRef
  10. Tunik, S, Aluclu, MU, Acar, A, Akkoc, H, Guzel, A, Alabalik, U, Akkus, M (2013) The effects of intravenous immunoglobulin on cerebral ischemia in rats: an experimental study. Toxicol Ind Health.
  11. Walberer, M, Nedelmann, M, Ritschel, N, Mueller, C, Tschernatsch, M, Stolz, E, Bachmann, G, Blaes, F, Gerriets, T (2010) Intravenous immunoglobulin reduces infarct volume but not edema formation in acute stroke. Neuroimmunomodulation 17: pp. 97-102 CrossRef
  12. Rodrigues, SF, Granger, DN (2014) Leukocyte-mediated tissue injury in ischemic stroke. Curr Med Chem 21: pp. 2130-2137 CrossRef
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• 刊物主题：Neurosciences; Neurology; Cardiology;
• 出版者：BioMed Central
• ISSN：2040-7378

文摘

Background The brain endothelium is a key component of the blood brain barrier which is compromised following ischemia, allowing infiltration of damaging immune cells and other inflammatory molecules into the brain. Intravenous immunoglobulin (IVIg) is known to reduce infarct size in a mouse model of experimental stroke. Findings Flow cytometry analysis showed that the protective effect of IVIg in ischemia and reperfusion injury in vivo is associated with reduced leukocyte infiltration, suggesting an involvement of the endothelium. In an in vitro model of ischemia, permeability analysis of the mouse brain endothelial cell line bEnd.3 revealed that IVIg prevented the loss of permeability caused by oxygen and glucose deprivation (OGD). In addition, western blot analysis of these brain endothelial cells showed that IVIg prevented the down-regulation of tight junction proteins claudin 5 and occludin and the decline in anti-apoptotic proteins Bcl-2 and Bcl-XL caused by OGD. Conclusion IVIg protects endothelial cells from ischemic insult. These studies support the use of IVIg as a pharmacological intervention for stroke therapy.