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Modulation of brain dead induced inflammation by vagus nerve stimulation

ABSTRACT: Because the vagus nerve is implicated in control of inflammation, we investigated if brain death causes impairment of the parasympathetic nervous system, hence contributing to inflammation. Brain death (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 harvested after 6h. Affymetrix chip- analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFα 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 TNFα 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, IL1β 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 TNFα through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE16483 | GEO | 2009/12/01

SECONDARY ACCESSION(S): PRJNA116319

REPOSITORIES: GEO

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Project description:The diagnosis and treatment trajectory of cancer can constitute a traumatic event because these can be perceived as sudden, catastrophic and life threatening. One common mental disorder following traumatic events is post-traumatic stress disorder (PTSD), described as reexperiencing of the event (e.g., having intrusive thoughts), having avoidance of trauma memories, emotional numbing, and experiencing hyperarousal symptoms. To date, and to the best of the investigator’s knowledge, few studies have focused on PTSD in advanced cancer, but the existing data show that these patients are at risk for experiencing PTSD symptoms. Among the early interventions for preventing PTSD in people confronted by traumatic events is group debriefing, the retelling of the event, receiving empathy and compassion, and being encouraged to express feelings. However, four meta-analyses found debriefing to be ineffective. A neuroscience-based and evidence-based alternative may be the Memory Structuring Intervention (MSI) that tries to shift trauma processing from a limbic, emotional and somatic level to a frontal-cortical, cognitive and verbal level of processing. The MSI tries to achieve this shift by teaching people confronted with traumatic events to chronologically organize the segments of the event, to verbally label feelings or somatic sensations rather than re-experience them, and to provide causal links between the event’s segments and causality to their feelings and sensations Since in males, sympathetic responses were more predictive of PTSD than in females , parasympathetic activation may be needed to be added to the MSI, for men. A main branch of the parasympathetic response is the vagus nerve, whose non-invasive index is Heart Rate Variability (HRV). One way to increase HRV, and thus parasympathetic activation, is through vagal breathing (i.e., deep, paced breathing). Therefore, adding to the MSI deep vagal breathing (VB) to reduce sympathetic hyperactivity, may increase connectivity between the amygdala and the frontal cortex. This may also increase the emotional regulation possibly yielded by the MSI, however in both genders. The effects of the MSI + vagal breathing on PTSD symptoms and on prognosis in advanced cancer patients receiving announcement of terminal cancer have never been investigated. Furthermore, whether reduced inflammation and increased emotional regulation may account for such effects needs to be investigated at the fundamental level. This project reflects the merging of neuroscience, psychooncology and psychoneuroimmunology for better understanding and treating cancer patients, as well as their partners.

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Modulation of brain dead induced inflammation by vagus nerve stimulation

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