Cerebral ischemia initiates an immediate innate immune response in neonates during cardiac surgery

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• 作者：Selma O Algra (1) (3) (4) (5)
  Kathelijne M Groeneveld (2)
  Alvin WL Schadenberg (3) (4)
  Felix Haas (1)
  Fabiola CM Evens (1)
  Jenny Meerding (3)
  Leo Koenderman (2)
  Nicolaas JG Jansen (4)
  Berent J Prakken (3)
  
• 关键词：Cardiac surgery ; Cerebral blood flow ; Hypothermia ; Inflammation ; Neonatal ischemia ; Randomized controlled trials
• 刊名：Journal of Neuroinflammation
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：10
• 期：1
• 全文大小：684KB
• 参考文献：1. Denker SP, Ji S, Dingman A, Lee SY, Derugin N, Wendland MF, Vexler ZS: Macrophages are comprised of resident brain microglia not infiltrating peripheral monocytes acutely after neonatal stroke. / J Neurochem 2007, 100:893-04. CrossRef
  2. Garcia JH, Liu KF, Yoshida Y, Chen S, Lian J: Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). / Am J Pathol 1994, 145:728-40.
  3. Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD: Experimental stroke induces massive, rapid activation of the peripheral immune system. / J Cereb Blood Flow Metab 2006, 26:654-65. CrossRef
  4. Perego C, Fumagalli S, De Simoni MG: Temporal pattern of expression and colocalization of microglia/macrophage phenotype markers following brain ischemic injury in mice. / J Neuroinflammation 2011, 8:174. CrossRef
  5. Wang LW, Chang YC, Lin CY, Hong JS, Huang CC: Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain. / Pediatr Res 2010, 68:41-7. CrossRef
  6. Iadecola C, Anrather J: The immunology of stroke: from mechanisms to translation. / Nat Med 2011, 17:796-08. CrossRef
  7. Montecucco F, Lenglet S, Gayet-Ageron A, Bertolotto M, Pelli G, Palombo D, Pane B, Spinella G, Steffens S, Raffaghello L, Pistoia V, Ottonello L, Pende A, Dallegri F, Mach F: Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischemic stroke. / Stroke 2010, 41:1394-404. CrossRef
  8. Urra X, Villamor N, Amaro S, Gomez-Choco M, Obach V, Oleaga L, Planas AM, Chamorro A: Monocyte subtypes predict clinical course and prognosis in human stroke. / J Cereb Blood Flow Metab 2009, 29:994-002. CrossRef
  9. Smith C, Emsley H, Gavin C, Georgiou R, Vail A, Barberan E, del Zoppo G, Hallenbeck J, Rothwell N, Hopkins S, Tyrrell P: Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. / BMC Neurol 2004, 4:2. CrossRef
  10. Bartha AI, Foster-Barber A, Miller SP, Vigneron DB, Glidden DV, Barkovich AJ, Ferriero DM: Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome. / Pediatr Res 2004, 56:960-66. CrossRef
  11. Nelson KB, Dambrosia JM, Grether JK, Phillips TM: Neonatal cytokines and coagulation factors in children with cerebral palsy. / Ann Neurol 1998, 44:665-75. CrossRef
  12. Xanthou M, Fotopoulos S, Mouchtouri A, Lipsou N, Zika I, Sarafidou J: Inflammatory mediators in perinatal asphyxia and infection. / Acta Paediatr Suppl 2002, 91:92-7. CrossRef
  13. Hasegawa K, Ichiyama T, Isumi H, Nakata M, Sase M, Furukawa S: NF-kappaB activation in peripheral blood mononuclear cells in neonatal asphyxia. / Clin Exp Immunol 2003, 132:261-64. CrossRef
  14. Bednarek N, Svedin P, Garnotel R, Favrais G, Loron G, Schwendiman L, Hagberg H, Morville P, Mallard C, Gressens P: Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia-ischemia: a potential marker of neonatal encephalopathy. / Pediatr Res 2012, 71:63-0. CrossRef
  15. Mirabelli-Badenier M, Braunersreuther V, Lenglet S, Galan K, Veneselli E, Viviani GL, Mach F, Montecucco F: Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury. / Eur J Clin Invest 2012, 42:784-94. CrossRef
  16. Fassbender K, Mossner R, Motsch L, Kischka U, Grau A, Hennerici M: Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke. / Stroke 1995, 26:1361-364. CrossRef
  17. Fassbender K, Mossner R, Motsch L, Kischka U, Grau A, Hennerici M: Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke. / Stroke 1995, 26:1361-364. CrossRef
  18. Worthmann H, Tryc AB, Goldbecker A, Ma YT, Tountopoulou A, Hahn A, Dengler R, Lichtinghagen R, Weissenborn K: The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome. / Cerebrovasc Dis 2010, 30:85-2. CrossRef
  19. Gregersen R, Lambertsen K, Finsen B: Microglia and macrophages are the major source of tumor necrosis factor in permanent middle cerebral artery occlusion in mice. / J Cereb Blood Flow Metab 2000, 20:53-5. CrossRef
  20. Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H: Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. / Stroke 1999, 30:2174-179. CrossRef
  21. Algra SO, Schouten AN, van Oeveren W, van der Tweel I, Schoof PH, Jansen NJ, Haas F: Low-flow antegrade cerebral perfusion attenuates early renal and intestinal injury during neonatal aortic arch reconstruction. / J Thorac Cardiovasc Surg 2012, 144:1323-328. CrossRef
  22. de Jager W, Prakken BJ, Bijlsma JW, Kuis W, Rijkers GT: Improved multiplex immunoassay performance in human plasma and synovial fluid following removal of interfering heterophilic antibodies. / J Immunol Methods 2005, 300:124-35. CrossRef
  23. Heimbeck I, Hofer TP, Eder C, Wright AK, Frankenberger M, Marei A, Boghdadi G, Scherberich J, Ziegler-Heitbrock L: Standardized single-platform assay for human monocyte subpopulations: Lower CD14+CD16++ monocytes in females. / Cytometry A 2010, 77:823-30.
  24. Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, Macpherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB: Nomenclature of monocytes and dendritic cells in blood. / Blood 2010, 116:e74-0. CrossRef
  25. Hughes SF, Hendricks BD, Edwards DR, Middleton JF: Tourniquet-applied upper limb orthopaedic surgery results in increased inflammation and changes to leukocyte, coagulation and endothelial markers. / PLoS One 2010, 5:e11846. CrossRef
  26. Hughes SF, Cotter MJ, Evans SA, Jones KP, Adams RA: Role of leucocytes in damage to the vascular endothelium during ischaemia-reperfusion injury. / Br J Biomed Sci 2006, 63:166-70.
  27. Zahler S, Massoudy P, Hartl H, Hahnel C, Meisner H, Becker BF: Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass. / Cardiovasc Res 1999, 41:722-30. CrossRef
  28. Mena H, Cadavid D, Rushing EJ: Human cerebral infarct: a proposed histopathologic classification based on 137 cases. / Acta Neuropathol 2004, 108:524-30. CrossRef
  29. Hess DC, Abe T, Hill WD, Studdard AM, Carothers J, Masuya M, Fleming PA, Drake CJ, Ogawa M: Hematopoietic origin of microglial and perivascular cells in brain. / Exp Neurol 2004, 186:134-44. CrossRef
  30. Okamura T, Ishibashi N, Kumar TS, Zurakowski D, Iwata Y, Lidov HG, Jonas RA: Hypothermic circulatory arrest increases permeability of the blood brain barrier in watershed areas. / Ann Thorac Surg 2010, 90:2001-008. CrossRef
  31. VanTeeffelen JW: How to prevent leaky vessels during reperfusion? Just keep that glycocalyx sealant in place! / Crit Care 2008, 12:167. CrossRef
  32. Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF: Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. / Circulation 2007, 116:1896-906. CrossRef
  33. Dimitrov S, Lange T, Born J: Selective mobilization of cytotoxic leukocytes by epinephrine. / J Immunol 2010, 184:503-11. CrossRef
  34. Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA: Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. / Science 1998, 282:480-83. CrossRef
  35. Denes A, Ferenczi S, Kovacs KJ: Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood- brain barrier damage and brain oedema independently of infarct size. / J Neuroinflammation 2011, 8:164. CrossRef
  36. Appachi E, Mossad E, Mee RB, Bokesch P: Perioperative serum interleukins in neonates with hypoplastic left-heart syndrome and transposition of the great arteries. / J Cardiothorac Vasc Anesth 2007, 21:184-90. CrossRef
  37. Hovels-Gurich HH, Schumacher K, Vazquez-Jimenez JF, Qing M, Huffmeier U, Buding B, Messmer BJ, von Bernuth G, Seghaye MC: Cytokine balance in infants undergoing cardiac operation. / Ann Thorac Surg 2002, 73:601-08. CrossRef
  38. McLean C, Ferriero D: Mechanisms of hypoxic-ischemic injury in the term infant. / Semin Perinatol 2004, 28:425-32. CrossRef
  39. Fernandez-Lopez D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, Wendland MF, Vexler ZS: Blood–brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat. / J Neurosci 2012, 32:9588-600. CrossRef
  40. Bronicki RA, Backer CL, Baden HP, Mavroudis C, Crawford SE, Green TP: Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. / Ann Thorac Surg 2000, 69:1490-495. CrossRef
  
• 作者单位：Selma O Algra (1) (3) (4) (5)
  Kathelijne M Groeneveld (2)
  Alvin WL Schadenberg (3) (4)
  Felix Haas (1)
  Fabiola CM Evens (1)
  Jenny Meerding (3)
  Leo Koenderman (2)
  Nicolaas JG Jansen (4)
  Berent J Prakken (3)
  
  1. Department of Pediatric Cardiothoracic Surgery, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584, Utrecht, EA, The Netherlands
  3. Department of Pediatric Immunology, Center for Cellular and Molecular Intervention, University Medical Center Utrecht, Lundlaan 6, 3584, Utrecht, EA, The Netherlands
  4. Pediatric Intensive Care Unit, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Lundlaan 6, 3584, Utrecht, EA, The Netherlands
  5. Pediatric Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands
  2. Department of Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, Utrecht, CX, The Netherlands
  
• ISSN：1742-2094

文摘

Background A robust inflammatory response occurs in the hours and days following cerebral ischemia. However, little is known about the immediate innate immune response in the first minutes after an ischemic insult in humans. We utilized the use of circulatory arrest during cardiac surgery to assess this. Methods Twelve neonates diagnosed with an aortic arch obstruction underwent cardiac surgery with cardiopulmonary bypass and approximately 30?minutes of deep hypothermic circulatory arrest (DHCA, representing cerebral ischemia). Blood samples were drawn from the vena cava superior immediately after DHCA and at various other time points from preoperatively to 24?hours after surgery. The innate immune response was assessed by neutrophil and monocyte count and phenotype using FACS, and concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, TNFα, sVCAM-1 and MCP-1 were assessed using multiplex immunoassay. Results were compared to a simultaneously drawn sample from the arterial cannula. Twelve other neonates were randomly allocated to undergo the same procedure but with continuous antegrade cerebral perfusion (ACP). Results Immediately after cerebral ischemia (DHCA), neutrophil and monocyte counts were higher in venous blood than arterial (P = 0.03 and P = 0.02 respectively). The phenotypes of these cells showed an activated state (both P <0.01). Most striking was the increase in the ‘non-classical-monocyte subpopulations (CD16intermediate; arterial 6.6% vs. venous 14%; CD16+ 13% vs. 22%, both P <0.01). Also, higher IL-6 and lower sVCAM-1 concentrations were found in venous blood (both P = 0.03). In contrast, in the ACP group, all inflammatory parameters remained stable. Conclusions In neonates, approximately 30?minutes of cerebral ischemia during deep hypothermia elicits an immediate innate immune response, especially of the monocyte compartment. This phenomenon may hold important clues for the understanding of the inflammatory response to stroke and its potentially detrimental consequences. Trial registration ClinicalTrial.gov: NCT01032876