sincalide and Postoperative-Complications

Delayed neurocognitive recovery (dNCR) is a common postoperative complication in geriatric surgical patients for which there is no efficacious therapy. Cholecystokinin octapeptide (CCK-8), an immunomodulatory peptide, regulates memory and learning. Here, we explored the effects and mechanism of action of CCK-8 on dNCR.. We applied laparotomy to establish a model of dNCR in aged mice. Morris water maze and fear conditioning tests were used to evaluate cognition. Immunofluorescence was used to detect the density of CCK-8, A1 reactive astrocytes, glutamatergic synapses, and activation of microglia in the hippocampus. Quantitative PCR was performed to determine mRNA levels of synapse-associated factors. A1 reactive astrocytes, activated microglia, and glutamatergic synapse-associated protein levels in the hippocampus were assessed by western blotting.. Administration of CCK-8 suppressed the activation of microglia, the induction of A1 reactive astrocytes, and the expression of tumor necrosis factor alpha, complement 1q, and interleukin 1 alpha in the hippocampus. Furthermore, it promoted glutamatergic synaptogenesis and neurocognitive recovery in aged dNCR model mice.. Our findings indicated that CCK-8 alleviated cognitive impairment and promoted glutamatergic synaptogenesis by inhibiting the induction of A1 reactive astrocytes and the activation of microglia. CCK-8 is, therefore, a potential therapeutic target for dNCR.

Topics: Animals; Astrocytes; Cognitive Dysfunction; Complement C1q; Fear; Female; Glutamates; Interleukin-1; Laparotomy; Macrophage Activation; Maze Learning; Mice; Mice, Inbred C57BL; Neurogenesis; Postoperative Complications; Sincalide; Synapses; Tumor Necrosis Factor-alpha

Many reports have been made on gallbladder dysfunction after gastric surgery. We reported that the gallbladder contractions were abolished after antrectomy. Our hypothesis is that preservation of the neural connection along gastric vessels maintains normal gallbladder function during fasting after antrectomy. Six dogs underwent antrectomy with preservation of the extrinsic nerves and six other dogs underwent conventional antrectomy with dissection of the extrinsic nerves and vessels. Laparotomy alone was performed on another six control dogs. Motor activities of the gallbladder and upper gastrointestinal tract were recorded by strain gauges in conscious dogs. Motilin and CCK-OP were used for pharmacological interventions. In conventional antrectomy, the amplitudes of the cyclic motor activity of the gallbladder and the stomach during fasting were significantly reduced, while this activity was maintained in dogs when extrinsic nerves were preserved. The coordination of the motor activity among the gallbladder, stomach and the duodenum was not impaired in the dogs when extrinsic nerves were preserved. The contractions of the gallbladder induced by exogenous motilin were reduced significantly in conventional antrectomy. Therefore, the preserved neural connection along the gastric vessels maintains normal gallbladder function in the fasting state even after distal gastrectomy.

Topics: Animals; Dogs; Duodenum; Female; Gallbladder; Gallbladder Emptying; Gastrectomy; Gastric Emptying; Gastrointestinal Motility; Male; Motilin; Periodicity; Postoperative Complications; Sincalide; Stomach; Vagotomy

The appearance of biliary pain after cholecystectomy in patients with normal ultrasonic and cholangiographic studies has been attributed to functional alterations of the Sphincter of Oddi. We performed dynamic cholescyntigraphic studies of the biliary tract in 32 cholecystectomized patients, at least six months after the operation: 27 were asymptomatic (control group) and 5 had clinical and laboratory findings suggesting temporary functional obstruction of the Sphincter of Oddi. In this group we demonstrated an emptying delay of the biliary tract that was modified by the IV infusion of Cholecystokinin Octapeptide. Biliary Cholescintigraphy appears as a good screening method to evaluate functional alterations of the Sphincter of Oddi.

Topics: Abdominal Pain; Biliary Dyskinesia; Cholecystectomy; Gastric Emptying; Humans; Postoperative Complications; Radionuclide Imaging; Sincalide; Sphincter of Oddi