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In preclinical rodent models, spinal cord injury (SCI) manifests as gastric vagal afferent dysfunction both acutely and chronically. However, the mechanism that underlies this dysfunction remains unknown. In the current study, we examined the effect of SCI on gastric nodose ganglia (NG) neuron excitability and on voltage-gated Na+ (Na V) channels expression and function in rats after an acute (i.e. 3-days) and chronic (i.e. 3-weeks) period. Rats randomly received either T3-SCI or sham control surgery 3-days or 3-weeks prior to experimentation as well as injections of 3% DiI solution into the stomach to identify gastric NG neurons. Single cell qRT-PCR was performed on acutely dissociated DiI-labeled NG neurons to measure Na V 1.7, Na V 1.8 and Na V 1.9 expression levels. The results indicate that all 3 channel subtypes decreased. Current- and voltage-clamp whole-cell patch-clamp recordings were performed on acutely dissociated DiI-labeled NG neurons to measure active and passive properties of C- and A-fibers as well as the biophysical characteristics of Na V 1.8 channels in gastric NG neurons. Acute and chronic SCI did not demonstrate deleterious effects on either passive properties of dissociated gastric NG neurons or biophysical properties of Na V 1.8. These findings suggest that although Na V gene expression levels change following SCI, Na V 1.8 function is not altered. The disruption throughout the entirety of the vagal afferent neuron has yet to be investigated. • SCI decreased the gene expression of Na V 1.7, Na V 1.8 and Na V 1.9 channels of rat gastric nodose ganglion (NG) neurons. • Downregulation of Na V channels within gastric vagal afferents may explain the reduction in vagal afferent sensitivity after SCI. • SCI did not impair either Na V 1.8 biophysical properties or the passive membrane properties of gastric NG neurons. • Further studies are necessary to identify the mechanisms responsible for diminished gastric vagal afferent signaling in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Background: The endogenous opioid peptide, nociception (Noc), contributes to the regulation of systemic blood pressure and regional blood flow. Recent clinical and animal studies have reported that Noc and its receptor (nociceptin/orphanin FQ [NOP]) are involved in inflammation and sepsis. The purpose of the present study was to examine the modulation of Ca2+ channels by Noc in acutely isolated stellate ganglion (SG) neurons from control and septic rats. Materials and methods: Sepsis was induced in male Sprague–Dawley rats via cecal ligation and puncture. SG neurons were isolated 24 and 72 h after sepsis induction. Thereafter, the concentration–response relationships for the Noc-stimulated NOP receptor Ca2+ current inhibition were determined using the whole-cell patch clamp technique. In addition, the Noc precursor (prepronociceptin [PNOC]) and NOP receptor messenger RNA (mRNA) levels were determined by quantitative real-time polymerase chain reaction, and PNOC protein levels were measured by Western blot analysis. Results: Comparison of the Noc concentration–response relationships in SG neurons from control and septic rats 24 h after sepsis revealed similar potency and efficacy. Moreover, 72 h after sepsis, neurons from control and septic rats exhibited an increased potency compared with both groups at the 24-h time point—an effect that was more pronounced in neurons from septic rats. PNOC mRNA levels were significantly greater in SG neurons isolated from septic rats compared with control neurons, but NOP receptor mRNA levels remained unchanged during the 72-h period. Conclusions: Our study demonstrates the cecal ligation and puncture model–induced temporal upregulation of components within the NOP receptor signaling pathway in rat sympathetic neurons. As SG neurons provide the main sympathetic input to the heart, an increased Noc release and potency during sepsis may compromise cardiovascular function. [Copyright &y& Elsevier]

Background: Cold storage in any of the commonly used preservation solutions is not always adequate for donation after cardiac death (DCD) liver grafts due to prolonged warm ischemic time. In this study, we used a third-generation perfluorocarbon (PFC), Oxycyte, for DCD liver graft preservation in a rat model. Materials and Methods: Twenty-eight rats (14 in each group) were used. Thirty minutes after cardiopulmonary arrest, livers were harvested and flushed with a cold and pre-oxygenated solution of either University of Wisconsin (UW) or UW + 20% PFC. After 8 h of cold preservation in either of the investigated solutions, liver graft specimens were analyzed for evidence of ischemic injury. Hemotoxylin and eosin staining (H and E), as well as immunohistochemical analysis with anti-cleaved caspase 3 antibody, was performed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the preservation solution were analyzed at 1 and 8 h during preservation. Results: In the PFC group, the degree of cell congestion, vacuolization and necrosis were all significantly less than in the UW group (P = 0.002–0.004). The number of cells with a positive cleaved caspase 3 antibody reaction was reduced by about 50% in comparison with the UW group (P < 0.006). The AST level in the PFC group was significantly less than in the UW group after 8 h of preservation (P < 0.048). Conclusion: The addition of PFC to UW solution significantly decreases the degree of histologic damage in rat DCD liver grafts. This preservation strategy can be potentially helpful for organ preservation after prolonged warm ischemia. [Copyright &y& Elsevier]