Rapid or Slow Time to Brain Death? Impact on Kidney Graft Injuries in an Allotransplantation Porcine Model

Kerforne, Thomas; Giraud, Sébastien; Danion, Jean-Marie; Thuillier, Raphaël; Couturier, Pierre; Hébrard, William; Mimoz, Olivier; Hauet, Thierry

doi:10.3390/ijms20153671

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…We previously demonstrated that ANOR could counteract DCD-induced IR lesions [22]. Herein, we investigated the hypothesis that DCD organs, when ANOR was used, were better than marginal organs and actually non inferior to standard DBD [24]. We tested this in a fully controlled preclinical model.…”

Section: Discussionmentioning

confidence: 99%

“…Brain death was reached by progressive insufflation of a balloon in the extradural space until a flat electroencephalogram was obtained [24]. Reanimation was maintained for 4 h before organ collection.…”

Section: Brain Death Modelmentioning

confidence: 99%

“…Warm ischemia (WI) after cardiac arrest was limited to 30 min (national recommendations) and ANOR was run for 4 h before organ collection. We also developed a brain death model, simulating a slow building encephalic pressure until brain death, followed by 4 h of reanimation [24].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Liver Quality after Circulatory Death versus Brain Death: A Comparative Preclinical Pig Model Study

Danion

Thuillier

Allain

et al. 2020

IJMS

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The current organ shortage in hepatic transplantation leads to increased use of marginal livers. New organ sources are needed, and deceased after circulatory death (DCD) donors present an interesting possibility. However, many unknown remains on these donors and their pathophysiology regarding ischemia reperfusion injury (IRI). Our hypothesis was that DCD combined with abdominal normothermic regional recirculation (ANOR) is not inferior to deceased after brain death (DBD) donors. We performed a mechanistic comparison between livers from DBD and DCD donors in a highly reproducible pig model, closely mimicking donor conditions encountered in the clinic. DCD donors were conditioned by ANOR. We determined that from the start of storage, pro-lesion pathways such as oxidative stress and cell death were induced in both donor types, but to a higher extent in DBD organs. Furthermore, pro-survival pathways, such as resistance to hypoxia and regeneration showed activation levels closer to healthy livers in DCD-ANOR rather than in DBD organs. These data highlight critical differences between DBD and DCD-ANOR livers, with an apparent superiority of DCD in terms of quality. This confirms our hypothesis and further confirms previously demonstrated benefits of ANOR. This encourages the expended use of DCD organs, particularly with ANOR preconditioning.

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Section: Discussionmentioning

confidence: 99%

Section: Brain Death Modelmentioning

confidence: 99%

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Evaluation of Liver Quality after Circulatory Death versus Brain Death: A Comparative Preclinical Pig Model Study

Danion

Thuillier

Allain

et al. 2020

IJMS

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“…In addition to Akt/GSK3β signaling pathway, Sirtuin 1 (SIRT1) signaling pathway can also increase Nrf2 transcription by deacetylating PGC1-α. 11,12 SIRT1, as the most studied enzyme among the 7 deacetylases in the Sir family, is widely present in various cells of the body and is closely related to the energy metabolism and reduction state of cells. 13,14 It is a new potential therapeutic target for diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

Lin¹,

Xu²,

Zheng³

et al. 2022

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Background: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and antiapoptotic properties, and exerts anti-diabetic pharmacological effects. Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism. Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated. Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and upregulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZinduced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells. Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.

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“…These strategies can be applied either immediately after organ procurement or after static cold storage (SCS). In any case, the oxygenation of the organs is an unsolved problem that attracts the interest and efforts of researchers in the field [26,27].…”

mentioning

confidence: 99%

New Insights in Molecular Mechanisms and Pathophysiology of Ischemia-Reperfusion Injury 2.0: An Updated Overview

Panisello‐Roselló

Roselló‐Catafau

Adam

2020

IJMS

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Rapid or Slow Time to Brain Death? Impact on Kidney Graft Injuries in an Allotransplantation Porcine Model

Cited by 9 publications

References 26 publications

Evaluation of Liver Quality after Circulatory Death versus Brain Death: A Comparative Preclinical Pig Model Study

Evaluation of Liver Quality after Circulatory Death versus Brain Death: A Comparative Preclinical Pig Model Study

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

New Insights in Molecular Mechanisms and Pathophysiology of Ischemia-Reperfusion Injury 2.0: An Updated Overview

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