Inflammatory immune responses in a reproducible mouse brain death model

Floerchinger, Bernhard and Yuan, Xiaodong and Jurisch, Anke and Timsit, Marc-Olivier and Ge, Xupeng and Lee, Ying-Lung and Schmid, Christof and Tullius, Stefan G. (2012) Inflammatory immune responses in a reproducible mouse brain death model. TRANSPLANT IMMUNOLOGY, 27 (1). pp. 25-29. ISSN 0966-3274,

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Abstract

Background: Brain death impairs donor organ quality and accelerates immune responses after transplantation. Detailed aspects of immune activation following brain death remain unclear. We have established a mouse model and investigated the immediate consequences of brain death and anesthesia on immune responses. Methods: C57JBI/6 mice (n = 6/group) were anesthetized with isoflurane (ISF) or ketamine/xylazine (KX); subsequently, animals underwent brain death induction and were followed for 3 h under continuous ventilation. Blood pressure was monitored continuously and animals were resuscitated with normal saline to achieve normotension. Immune activation in brain dead animals was analyzed by IFN-gamma-ELispot, MLR, and flow-cytometry. Sham-operated and naive animals served as controls. Results: Blood pressure remained stable in both BD/KX and BD/ISF animals during the 3 h observation time. Brain death was linked to systemic immune activation: IFN gamma-expression of splenocytes and lymphocyte proliferation rates was significantly elevated subsequent to brain death (p<0.02, <0.01); T-cell activation markers CD28 and CD69 had increased in brain dead animals (p<0.03, <0.02). Isoflurane treatment in sham controls throughout the observation period (3.5 h) revealed anesthesia associated IFN gamma-expression and lymphocyte activation which were not observed when animals were treated with ketamine/xylazine (p<0.04, <0.009). Conclusions: This study reports on a reproducible and hemodynamically stable brain death mouse model. Hemodynamic stability was not impacted through either isoflurane or ketamine/xylazine induction. Of clinical relevance, prolonged anesthesia with isoflurane had been linked to pro-inflammatory cytokine activation. Brain death caused systemic immune activation in organ donors. (C) 2012 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: PROINFLAMMATORY CYTOKINES; MECHANICAL VENTILATION; ISOFLURANE ANESTHESIA; ALVEOLAR MACROPHAGES; CARDIAC-FUNCTION; DONOR ORGANS; IN-VIVO; MICE; RAT; ACTIVATION; Immune response; Anesthesia; Brain death
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 May 2020 05:11
Last Modified: 08 May 2020 05:11
URI: https://pred.uni-regensburg.de/id/eprint/18349

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