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Brain Death-Induced Inflammation: Possible Role of the Cholinergic Anti-inflammatory Pathway

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The Brain-Dead Organ Donor

Abstract

Brain death is accompanied by a systemic inflammatory response leading to inflammation in end-organs. Experimental studies in rats have demonstrated that brain death per se has adverse effects on immediate renal function in recipients. This points out that brain death-induced inflammation is an undesired event, affecting organ function and therefore should be prevented or limited in brain-dead donors. Apart from tissue ischemia, cytokine release from the brain and increased intestinal permeability leading to systemic immune activation may explain brain death-induced inflammation. Although not thoroughly studied, failure of the cholinergic anti-inflammatory pathway during brain death represents a further alternative to explain excessive inflammation in brain-dead donors. In this chapter, we discuss the inflammatory reflex, show the beneficial effect of activating the cholinergic anti-inflammatory pathway in a variety of experimental models including brain death, and finally we discuss the different modalities for activating the cholinergic anti-inflammatory pathway as therapeutic interventions. We conclude that stimulation of the anti-inflammatory pathway in brain-dead donors has the potential to reduce the proinflammatory status of the graft and thus to improve organ quality. Hence, more preclinical studies are warranted to assess the benefits, or adverse effect of this modality on organ function before its implementation as new donor management strategy into clinical practice.

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Authors and Affiliations

  1. Department of Medicine V (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, Medical Faculty Mannheim, Ruprecht-Karls University, Heidelberg, Mannheim, Germany

    Simone Hoeger Ph.D. & Benito A. Yard Ph.D.

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  1. Simone Hoeger Ph.D.
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  2. Benito A. Yard Ph.D.
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Correspondence to Simone Hoeger Ph.D. .

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Editors and Affiliations

  1. Tampa VA Medical Center, Surgery, University of South Florida, Bruce B. Downs Blvd 12901, Tampa, 33612, Florida, USA

    Dimitri Novitzky

  2. Thomas E. Starzl Transplantation Institu, Department of Surgery, University of Pittsburgh Medical Center, Lothrop Street 200, Pittsburgh, 15213, Pennsylvania, USA

    David K C Cooper

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Hoeger, S., Yard, B.A. (2013). Brain Death-Induced Inflammation: Possible Role of the Cholinergic Anti-inflammatory Pathway. In: Novitzky, D., Cooper, D. (eds) The Brain-Dead Organ Donor. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4304-9_11

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  • DOI: https://doi.org/10.1007/978-1-4614-4304-9_11

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