Brain Death Induces Inflammation in the Donor Intestine

Koudstaal, Lyan G.; Hart, Nils A 't; Ottens, Petra J.; Berg, Anke van den; Ploeg, Rutger J.; Goor, Harry van; Leuvenink, Henri G. D.

doi:10.1097/tp.0b013e31817ba53a

Cited by 36 publications

(23 citation statements)

References 22 publications

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“…CNS-derived cytokines are then free to interact at receptors within the systemic tissues, inducing local inflammation and “priming” organs for further injury [81, 85]. The importance of brain injury-derived cytokinaemia was recently demonstrated by Graetz et al, who reviewed compartmental levels of IL-6 in SAH and found that elevated plasma IL-6 is associated with increased mortality [72].…”

Section: Stage One Of Potential Organ Injury: Brain Injurymentioning

confidence: 99%

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Watts

Thom

Fraser

2013

Journal of Transplantation

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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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Section: Stage One Of Potential Organ Injury: Brain Injurymentioning

confidence: 99%

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Watts

Thom

Fraser

2013

Journal of Transplantation

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“…HRV could not be measured in the BD + STIM group because of electrical interference of the ECG during electrical vagus nerve stimulation. induces the expression of pro-inflammatory genes in the small intestine (9)(10)(11)31), we first investigated if vagus stimulation resulted in global changes in gene expression profiles in the small intestine of BD animals.…”

Section: Blood Pressure Monitoring and Heart Rate Variability (Hrv)mentioning

confidence: 99%

Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

Hoeger

Bergstraesser

Selhorst

et al. 2010

American Journal of Transplantation

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Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chipanalysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFa concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFa concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1b and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFa through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.

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“…41 Research using experimental BD models reported inflammatory changes and progressive organ dysfunction after BD. [42][43][44] At the clinical level, biopsies of livers from BD patients revealed that later organ harvest increased the expression of apoptosis-related genes and the presence of inflammatory phenomena. 45,46 In light of this evidence, shorter intervals between the establishment of BD and organ extraction would result in less exposure to the systemic inflammation triggered by BD, reducing organ loss, increasing organ quality, and significantly improving graft survival rate, while shortening the gap between organ supply and demand.…”

Section: Fig 2 (A)mentioning

confidence: 99%

S100B Protein May Detect Brain Death Development after Severe Traumatic Brain Injury

Egea-Guerrero

Murillo-Cabezas

Gordillo-Escobar

et al. 2013

Journal of Neurotrauma

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Despite improvements in the process of organ donation and transplants, the number of organ donors is progressively declining in developed countries. Therefore, the early detection of patients at risk for brain death (BD) is a priority for transplant teams seeking more efficient identification of potential donors. In the extensive literature on S100B as a biomarker for traumatic brain injury (TBI), no evidence appears to exist on its prognostic capacity as a predictor of BD after severe TBI. The objective of this study is to assess the value of including acute S100B levels in standard clinical data as an early screening tool for BD after severe TBI. This prospective study included patients with severe TBI (Glasgow Coma Scale score [GCS] £ 8) admitted to our Neurocritical Care Unit over a 30 month period. We collected the following clinical variables: age, gender, GCS score, pupillary alterations at admission, hypotension and pre-hospital desaturation, CT scan results, isolated TBI or other related injuries, Injury Severity Score (ISS), serum S100B levels at admission and 24 h post-admission, and a final diagnosis regarding BD. Of the 140 patients studied, 11.4% developed BD and showed significantly higher S100B concentrations ( p < 0.001). Multivariate analysis showed that bilateral unresponsive mydriasis at admission and serum S100B at 24 h post-admission had odds ratios (ORs) of 21.35 ( p = 0.005) and 4.9 ( p = 0.010), respectively. The same analysis on patients with photomotor reflex in one pupil at admission left only the 24 h S100B sample in the model (OR = 15.5; p = 0.009). Receiver operating characteristics (ROC) curve analysis on this group showed the highest area under the curve (AUC) (0.86; p = 0.001) for 24 h S100B determinations. The cut off was set at 0.372 lg/L (85.7% sensitivity, 79.3% specificity, positive predictive value [PPV] = 18.7% and negative predictive value [NPV] = 98.9%). This study shows that pupillary responsiveness at admission, as well as 24 h serum S100B levels, could serve as screening tools for the early detection of patients at risk for BD after severe TBI.

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Brain Death Induces Inflammation in the Donor Intestine

Abstract: These data show the early occurrence of intestinal inflammation and apoptosis after BD induction. These events may ultimately have a negative influence on the outcome of intestinal transplantation.

Cited by 36 publications

References 22 publications

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

S100B Protein May Detect Brain Death Development after Severe Traumatic Brain Injury

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