Both inflammatory processes and glutamatergic systems have been implicated in the pathophysiology of mood-related disorders. However, the role of caspase-1, a classic inflammatory caspase, in behavioral responses to chronic stress remains largely unknown. To address this issue, we examined the effects and underlying mechanisms of caspase-1 on preclinical murine models of depression. We found that loss of caspase-1 expression in Caspase-1−/− knockout mice alleviated chronic stress-induced depression-like behaviors, whereas overexpression of caspase-1 in the hippocampus of wild-type (WT) mice was sufficient to induce depression- and anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic neurotransmission and decreased surface expression of glutamate receptors in hippocampal pyramidal neurons of WT mice, but not Caspase-1−/− mice. Importantly, pharmacological inhibition of caspase-1-interleukin-1β (IL-1β) signaling pathway prevented the depression-like behaviors and the decrease in surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both depression- and anxiety-like behaviors can be mimicked by exogenous intracerebroventricular (i.c.v.) administration of IL-1β in both WT and Caspase-1−/− mice. Taken together, our findings demonstrate that an increase in the caspase-1/IL-1β axis facilitates AMPAR internalization in the hippocampus, which dysregulates glutamatergic synaptic transmission, eventually resulting in depression-like behaviors. These results may represent an endophenotype for chronic stress-induced depression.
Background: Established closure techniques for the pancreatic remnant after distal pancreatectomy include stapler, suture and anastomotic closure. However, controversy remains regarding the ideal technique; therefore, the aim of this study was to compare closure techniques and risk of postoperative pancreatic fistula (POPF).Methods: A systematic review was carried out according to PRISMA guidelines for studies published before January 2014 that compared at least two closure techniques for the pancreatic remnant in distal pancreatectomy. A random-effects model was constructed using weighted odds ratios (ORs).Results: Thirty-seven eligible studies matched the inclusion criteria and 5252 patients who underwent distal pancreatectomy were included. The primary outcome measure, the POPF rate, ranged 0 from to 70 per cent. Meta-analysis of the 31 studies comparing stapler versus suture closure showed that the stapler technique had a significantly lower rate of POPF, with a combined OR of 0⋅77 (95 per cent c.i. 0⋅61 to 0⋅98; P = 0⋅031). Anastomotic closure was associated with a significantly lower POPF rate than suture closure (OR 0⋅55, 0⋅31 to 0⋅98; P = 0⋅042). Combined stapler and suture closure had significantly lower POPF rates than suture closure alone, but no significant difference compared with stapler closure alone. Conclusion:The use of stapler closure or anastomotic closure for the pancreatic remnant after distal pancreatectomy significantly reduces POPF rates compared with suture closure. The combination of stapler and suture closure shows superiority over suture closure alone.
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