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Review

The blood-brain barrier dysfunction in sepsis

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Article: 1840912 | Received 28 Aug 2020, Accepted 19 Oct 2020, Published online: 15 Dec 2020

References

  • Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). Jama. 2016;315(8):1–10. Epub 2016/02/24. doi:10.1001/jama.2016.0287.
  • CDC. Data & Reports. 2020 [updated August 20, 2020]; Available from: cdc.gov/sepsis/datareports/index.html.
  • Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. Jama. 2018;319(1):62–75. doi:10.1001/jama.2017.17687.
  • Prescott HC, Carmichael AG, Langa KM, Gonzalez R, Iwashyna TJ. Paths into sepsis: trajectories of presepsis healthcare use. Ann Am Thorac Soc. 2019;16(1):116–123. Epub 2018/09/14. doi:10.1513/AnnalsATS.201806-391OC.
  • Prescott HC, Osterholzer JJ, Langa KM, Angus DC, Iwashyna TJ. Late mortality after sepsis: propensity matched cohort study. BMJ (Clinical Research Ed). 2016;353:i2375. Epub 2016/05/18
  • Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. Jama. 2010;304(16):1787–1794. doi:10.1001/jama.2010.1553.
  •  Kumar S, Ingle H, Prasad DV, Kumar H. Recognition of bacterial infection by innate immune sensors. Crit Rev Microbiol. 2013;39(3):229–246. doi:10.3109/1040841X.2012.706249.
  • Heckenberg SG, Brouwer MC, van de Beek D. Bacterial meningitis. Handb Clin Neurol. 2014;121:1361–1375. Epub 2013/12/25.
  • Sellner J, Täuber MG, Leib SL. Chapter 1 - Pathogenesis and pathophysiology of bacterial CNS infections. Karen LR, Allan RT editors. Handbook of Clinical Neurology. Elsevier, Netherlands; 2010, 1–16.
  • Mook-Kanamori BB, Geldhoff M, van der Poll T, van de Beek D. Pathogenesis and pathophysiology of pneumococcal meningitis. Clin Microbiol Rev. 2011;24(3):557–591. Epub 2011/07/08.
  • Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science (New York, NY). 2010;327(5963):291–295. Epub 2010/01/16. doi:10.1126/science.1183021.
  • Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence. 2014;5(1):36–44. Epub 2013/06/19. doi:10.4161/viru.25436.
  • Lu B, Wang C, Wang M, Li W, Chen F, Tracey KJ, Wang H. Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review. Expert Rev Clin Immunol. 2014;10(6):713–727. Epub 2014/04/22. doi:10.1586/1744666X.2014.909730.
  • Annane D, Sharshar T. Cognitive decline after sepsis. Lancet Respir Med. 2015;3(1):61–69. doi:10.1016/S2213-2600(14)70246-2.
  • Sharshar T, Carlier R, Bernard F, Guidoux C, Brouland J-P, Nardi O, de la Grandmaison GL, Aboab J, Gray F, Menon D, et al. Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med. 2007;33(5):798–806. Epub 2007/03/23. doi:10.1007/s00134-007-0598-y.
  • Westhoff D, Engelen-Lee JY, Hoogland ICM, Aronica EMA, van Westerloo DJ, van de Beek D, van Gool WA. Systemic infection and microglia activation: a prospective postmortem study in sepsis patients. Immunity Ageing. 2019 Epub 2019/08/07;16(1):18. doi:10.1186/s12979-019-0158-7.
  • Zhao G-JG-J, Li D, Zhao Q, Lian J, Hu -T-T, Hong G-L, Yao Y-M, Lu Z-Q. Prognostic value of plasma tight-junction proteins for sepsis in emergency department: an observational study. Shock. 2016;45(3):326–332. doi:10.1097/SHK.0000000000000524.
  • Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15(4):275–292. Epub 2016/01/23
  • Erickson MA, Banks WA. Neuroimmune axes of the blood-brain barriers and blood-brain interfaces: bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol Rev. 2018;70(2):278–314. Epub 2018/03/03. doi:10.1124/pr.117.014647.
  • Barichello TCA, Hasbun R, Morales R. An overview of the blood-brain barrier. In: Barichello T, editor. Blood-brain barrier. New York (NY): Humana Press; 2019. p. 1–8.
  • Zeng H, He X, Tuo QH, Liao DF, Zhang GQ, Chen JX. LPS causes pericyte loss and microvascular dysfunction via disruption of Sirt3/angiopoietins/Tie-2 and HIF-2α/Notch3 pathways. Sci Rep. 2016;6:20931. Epub 2016/02/13..
  • Wu Y, Li P, Goodwin AJ, Cook JA, Halushka PV, Zingarelli B, Fan H. miR-145a regulation of pericyte dysfunction in a murine model of sepsis. J Infect Dis. 2020;222(6):1037–1045. Epub 2020/04/15. doi:10.1093/infdis/jiaa184.
  • Danielski LG, Giustina AD, Badawy M, Barichello T, Quevedo J, Dal-Pizzol F, Petronilho F. Brain barrier breakdown as a cause and consequence of neuroinflammation in sepsis. Mol Neurobiol. 2018;55(2):1045–1053. Epub 2017/01/17. doi:10.1007/s12035-016-0356-7.
  • Lee WL, Slutsky AS. Sepsis and endothelial permeability. N Engl J Med. 2010;363(7):689–691. Epub 2010/09/08. doi:10.1056/NEJMcibr1007320.
  • Barichello T, Generoso JS, Silvestre C, Costa CS, Carrodore MM, Cipriano AL, Michelon CM, Petronilho F, Dal-Pizzol F, Vilela MC, et al. Circulating concentrations, cerebral output of the CINC-1 and blood–brain barrier disruption in Wistar rats after pneumococcal meningitis induction. Eur J Clin Microbiol Infect Dis. 2012;31(8):2005–2009. Epub 2012/02/04. doi:10.1007/s10096-011-1533-2.
  • Giridharan VV, Collodel A, Generoso JS, Scaini G, Wassather R, Selvaraj S, Hasbun R, Dal-Pizzol F, Petronilho F, Barichello T, et al. Neuroinflammation trajectories precede cognitive impairment after experimental meningitis-evidence from an in vivo PET study. J Neuroinflammation. 2020;17(1):5. Epub 2020/01/07. doi:10.1186/s12974-019-1692-0.
  • Biswal S, Remick DG. Sepsis: redox mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2007;9(11):1959–1961. Epub 2007/08/23
  • Barichello T, Generoso JS, Simões LR, Elias SG, Quevedo J. Role of oxidative stress in the pathophysiology of pneumococcal meningitis. Oxid Med Cell Longev. 2013;2013:371465. Epub 2013/06/15. doi:10.1155/2013/371465.
  • Zhang RY, Zhang H, Huang J, Qu H-P, Tang Y-Q. Angiogenic factors in sepsis: are we ready for the new therapeutic era? Critical Care (London, England). 2014;18(1):403. Epub 2014/01/31. doi:10.1186/cc13710.
  • Masciantonio MG, Lee CKS, Arpino V, Mehta S, Gill SE. The balance between metalloproteinases and TIMPs: critical regulator of microvascular endothelial cell function in health and disease. Prog Mol Biol Transl Sci. 2017;147:101–131. Epub 2017/04/18.
  • Yazdan-Ashoori P, Liaw P, Toltl L, Webb B, Kilmer G, Carter DE, Fraser DD. Elevated plasma matrix metalloproteinases and their tissue inhibitors in patients with severe sepsis. J Crit Care. 2011;26(6):556–565. Epub 2011/03/29. doi:10.1016/j.jcrc.2011.01.008.
  • Erikson K, Tuominen H, Vakkala M, Liisanantti JH, Karttunen T, Syrjälä H, Ala-Kokko TI. Brain tight junction protein expression in sepsis in an autopsy series. Critical Care (London, England). 2020;24(1):385. Epub 2020/07/01. doi:10.1186/s13054-020-03101-3.
  • Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock–a review of laboratory models and a proposal. J Surg Res. 1980;29(2):189–201. doi:10.1016/0022-4804(80)90037-2.
  • Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW, Bland KI, Chaudry IH. Cecal ligation and puncture. Shock (Augusta, Ga). 2005;24(Suppl 1):52–57. Epub 2005/12/24. doi:10.1097/01.shk.0000191414.94461.7e.
  • Zantl N, Uebe A, Neumann B, Wagner H, Siewert J-R, Holzmann B, Heidecke C-D, Pfeffer K. Essential role of gamma interferon in survival of colon ascendens stent peritonitis, a novel murine model of abdominal sepsis. Infect Immun. 1998;66(5):2300–2309. Epub 1998/05/09. doi:10.1128/IAI.66.5.2300-2309.1998.
  • Weinstein WM, Onderdonk AB, Bartlett JG, Gorbach SL. Experimental intra-abdominal abscesses in rats: development of an experimental model. Infect Immun. 1974;10(6):1250–1255. Epub 1974/12/01. doi:10.1128/IAI.10.6.1250-1255.1974.
  • Deitch EA. Animal models of sepsis and shock: a review and lessons learned. Shock (Augusta, Ga). 1998;9(1):1–11. Epub 1998/02/18. doi:10.1097/00024382-199801000-00001.
  • Comim CM, Vilela MC, Constantino LS, Petronilho F, Vuolo F, Lacerda-Queiroz N, Rodrigues DH, da Rocha JL, Teixeira AL, Quevedo J, et al. Traffic of leukocytes and cytokine up-regulation in the central nervous system in sepsis. Intensive Care Med. 2011;37(4):711–718. doi:10.1007/s00134-011-2151-2.
  • Mina F, Comim CM, Dominguini D, Cassol-Jr OJ, Dall`Igna DM, Ferreira GK, Silva MC, Galant LS, Streck EL, Quevedo J, et al. Il1-β involvement in cognitive impairment after sepsis. Mol Neurobiol. 2014;49(2):1069–1076. Epub 2013/11/16. doi:10.1007/s12035-013-8581-9.
  • Dal-Pizzol F, Rojas HA, Dos Santos EM, Vuolo F, Constantino L, Feier G, Pasquali M, Comim CM, Petronilho F, Gelain DP, et al. Matrix metalloproteinase-2 and metalloproteinase-9 activities are associated with blood–brain barrier dysfunction in an animal model of severe sepsis. Mol Neurobiol. 2013;48(1):62–70. Epub 2013/03/13. doi:10.1007/s12035-013-8433-7.
  • Yu H-YH-Y, Cai Y-B, Liu Z. Activation of AMPK improves lipopolysaccharide-induced dysfunction of the blood–brain barrier in mice. Brain Injury. 2015;29(6):777–784. Epub 2015/03/21. doi:10.3109/02699052.2015.1004746.
  • Vutukuri R, Brunkhorst R, Kestner R-I, Hansen L, Bouzas NF, Pfeilschifter J, Devraj K, Pfeilschifter W. Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption. J Neurochem. 2018;144(2):172–185. doi:10.1111/jnc.14236.
  • Griton M, Dhaya I, Nicolas R, Raffard G, Periot O, Hiba B, Konsman JP. Experimental sepsis-associated encephalopathy is accompanied by altered cerebral blood perfusion and water diffusion and related to changes in cyclooxygenase-2 expression and glial cell morphology but not to blood-brain barrier breakdown. Brain Behav Immun. 2020;83:200–213. doi:10.1016/j.bbi.2019.10.012.
  • Flierl MA, Stahel PF, Rittirsch D, Huber-Lang M, Niederbichler AD, Hoesel LM, Touban BM, Morgan SJ, Smith WR, Ward PA, et al. Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis. Crit Care. 2009;13(1):6. doi:10.1186/cc7710.
  • Bozza FA, Garteiser P, Oliveira MF, Doblas S, Cranford R, Saunders D, Jones I, Towner RA, Castro-Faria-Neto HC. Sepsis-associated encephalopathy: a magnetic resonance imaging and spectroscopy study. J Cereb Blood Flow Metab. 2010;30(2):440–448. doi:10.1038/jcbfm.2009.215.
  • Reis PA, Alexandre PCB, D’Avila JC, Siqueira LD, Antunes B, Estato V, Tibiriça EV, Verdonk F, Sharshar T, Chrétien F, et al. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction. Brain Behav Immun. 2017;60:293–303. doi:10.1016/j.bbi.2016.11.006.
  • Silva AYO, Amorim ÉA, Barbosa-Silva MC, Lima MN, Oliveira HA, Granja MG, Oliveira KS, Fagundes PM, Neris RLS, Campos RMP, et al. Mesenchymal stromal cells protect the blood-brain barrier, reduce astrogliosis, and prevent cognitive and behavioral alterations in surviving septic mice. Crit Care Med. 2020;48(4):e290–e8. doi:10.1097/CCM.0000000000004219.
  • Barichello T, Sayana P, Giridharan VV, Arumanayagam AS, Narendran B, Della Giustina A, Petronilho F, Quevedo J, Dal-Pizzol F. Long-term cognitive outcomes after sepsis: a translational systematic review. Mol Neurobiol. 2019;56(1):186–251. Epub 2018/04/25.
  • Hughes CG, Pandharipande PP, Thompson JL, Chandrasekhar R, Ware LB, Ely EW, Girard TD. Endothelial activation and blood-brain barrier injury as risk factors for delirium in critically Ill patients. Crit Care Med. 2016;44(9):e809–17. Epub 2016/04/19. doi:10.1097/CCM.0000000000001739.
  • Skibsted S, Jones AE, Puskarich MA, Arnold R, Sherwin R, Trzeciak S, Schuetz P, Aird WC, Shapiro NI. Biomarkers of endothelial cell activation in early sepsis. Shock (Augusta, Ga). 2013;39(5):427–432. Epub 2013/03/26. doi:10.1097/SHK.0b013e3182903f0d.
  • Mikacenic C, Hahn WO, Price BL, Harju-Baker S, Katz R, Kain KC, Himmelfarb J, Liles WC, Wurfel MM. Biomarkers of endothelial activation are associated with poor outcome in critical illness. PloS One. 2015;10(10):e0141251. Epub 2015/10/23. doi:10.1371/journal.pone.0141251.
  • Ikeda M, Matsumoto H, Ogura H, Hirose T, Shimizu K, Yamamoto K, Maruyama I, Shimazu T. Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis. J Crit Care. 2018;43:48–53. Epub 2017/08/28. doi:10.1016/j.jcrc.2017.07.049.
  • Bloomfield SM, McKinney J, Smith L, Brisman J. Reliability of S100B in predicting severity of central nervous system injury. Neurocrit Care. 2007;6(2):121–138. doi:10.1007/s12028-007-0008-x.
  • Wu L, Feng Q, Ai ML, Deng SY, Liu ZY, Huang L, Ai YH, Zhang L. The dynamic change of serum S100B levels from day 1 to day 3 is more associated with sepsis-associated encephalopathy. Sci Rep. 2020;10(1):7718. Epub 2020/05/10.
  • Erikson K, Ala-Kokko TI, Koskenkari J, Liisanantti JH, Kamakura R, Herzig KH, Syrjälä H. Elevated serum S-100β in patients with septic shock is associated with delirium. Acta Anaesthesiol Scand. 2019;63(1):69–73. Epub 2018/08/07. doi:10.1111/aas.13228.

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