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Time-dependent changes in donor brain death related processes.

T A Schuurs1, A M Morariu, P J Ottens

  • 1Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands. t.a.schuurs@chir.umcg.nl

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|October 26, 2006
PubMed
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Brain death rapidly triggers inflammation and protective gene expression in donor kidneys. Early chemokine increases, not hypoxia, initiate this cascade, impacting kidney transplant outcomes.

Area of Science:

  • Nephrology
  • Transplantation Immunology
  • Molecular Biology

Background:

  • Brain death (BD) negatively impacts kidney graft function and survival.
  • Kidney donor brains exhibit inflammation, coagulation, and cytoprotective gene activation.
  • Understanding the temporal progression of these BD-related renal processes is crucial.

Purpose of the Study:

  • To investigate the time-course progression of renal processes following brain death.
  • To identify early molecular and cellular changes in donor kidneys after BD.
  • To determine the initial triggers of the inflammatory cascade in BD kidneys.

Main Methods:

  • Time-course analysis of gene expression (E-selectin, MCP-1, IL-6, HO-1, HSP70, NF-kappaB, Egr-1) in kidneys post-BD.
  • Assessment of infiltrating granulocytes and reactive oxygen species formation.

Related Experiment Videos

  • Measurement of serum cytokines (MCP-1, KC-protein) at various time points after BD.
  • Comparison with sham-operated control animals.
  • Main Results:

    • Massive upregulation of proinflammatory genes (E-selectin, MCP-1, IL-6) and inducers (NF-kappaB, Egr-1) within 0.5 hours post-BD.
    • Increased granulocyte infiltration observed from 0.5 hours onwards.
    • Early induction of protective genes (HO-1, HSP70) within 0.5 hours.
    • Significant elevation of MCP-1 and KC-protein in serum starting at 0.5 hours.
    • Reactive oxygen species formation detected only in later BD phases.

    Conclusions:

    • Brain death rapidly induces both proinflammatory and stress-induced protective responses in donor kidneys.
    • Early changes during BD induction, not hypoxia, appear to trigger these processes.
    • Elevated systemic chemokines (MCP-1, KC) likely initiate the inflammatory cascade in brain-dead donor kidneys.