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. 2013:2013:521369.
doi: 10.1155/2013/521369. Epub 2013 Apr 15.

Inflammatory signalling associated with brain dead organ donation: from brain injury to brain stem death and posttransplant ischaemia reperfusion injury

Affiliations

Inflammatory signalling associated with brain dead organ donation: from brain injury to brain stem death and posttransplant ischaemia reperfusion injury

Ryan P Watts et al. J Transplant. 2013.

Abstract

Brain death is associated with dramatic and serious pathophysiologic changes that adversely affect both the quantity and quality of organs available for transplant. To fully optimise the donor pool necessitates a more complete understanding of the underlying pathophysiology of organ dysfunction associated with transplantation. These injurious processes are initially triggered by catastrophic brain injury and are further enhanced during both brain death and graft transplantation. The activated inflammatory systems then contribute to graft dysfunction in the recipient. Inflammatory mediators drive this process in concert with the innate and adaptive immune systems. Activation of deleterious immunological pathways in organ grafts occurs, priming them for further inflammation after engraftment. Finally, posttransplantation ischaemia reperfusion injury leads to further generation of inflammatory mediators and consequent activation of the recipient's immune system. Ongoing research has identified key mediators that contribute to the inflammatory milieu inherent in brain dead organ donation. This has seen the development of novel therapies that directly target the inflammatory cascade.

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Figures

Figure 1
Figure 1
Primary mediators of peri-transplant related inflammation. Al: aldosterone, APC: antigen presenting cell, APP: acute phase proteins, AT2: angiotensin II, BV: biliverdin, C: complement, CA: catecholamines, CAM: cellular adhesion molecule, Casp-1: caspase 1, CI: cellular inflammation, CO: carbon monoxide, Coag: coagulation, Endo: endothelial cells, Eo: eosinophils, EPO: erythropoietin, ET: endothelin, F2: factor II (Thrombin), Fe: iron, Fibro: fibrosis, FN: fibronectin, FR: free radicals, HI: humoral immunity, HIF: hypoxia inducible factor, HO1: heme oxygenase 1, IFN: interferon, Ig: immunoglobulin, IL: interleukin, IL1RA: interleukin 1 receptor antagonist, Infl: inflammation, IP: interferon-γ-induced protein, IRI: ischaemia reperfusion injury, MMP: matrixmetalloproteinases, MRD: margination/rolling/diapedesis, NE: new antigens/neoepitopes, Neut: neutrophils, O2: oxygen, Perox: peroxidation, Sel: selectin, SmMc: smooth muscle contraction, TF: tissue factor, TGF: transforming growth factor, TH1: type 1 helper T-cell, TH17: type 17 helper T-cell, TH2: type 2 helper T-cell, TNF: tumour necrosis factor, Treg: regulatory T-cell, VC: vasoconstriction, VEGF: vascular endothelial growth factor.
Figure 2
Figure 2
Interaction of homeostatic mechanisms after BD. ALI: acute lung injury,   AM: alveolar macrophage, ARDS: acute respiratory distress syndrome, CaO2: arterial oxygen content, BBB: blood brain barrier, BS: brain stem, CHO: carbohydrate, CNS: central nervous system, CO: cardiac output, DO2: oxygen delivery, NPO: neurogenic pulmonary oedema, PNS: parasympathetic nervous system, PVR: pulmonary vascular resistance, ROS: reactive oxygen species, VC: vasoconstriction.

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