Loading...
Please wait, while we are loading the content...
Similar Documents
CPSI-121 pharmacologically prevents intestinal barrier dysfunction after cutaneous burn through a vagus nerve-dependent mechanism
| Content Provider | Scilit |
|---|---|
| Author | Krzyzaniak, Michael Ortiz-Pomales, Yan Lopez, Nicole Reys, Luiz Guilherme Cheadle, Gerald Wolf, Paul Eliceiri, Brian Bansal, Vishal Baird, Andrew Coimbra, Raul |
| Copyright Year | 2012 |
| Description | Journal: The Journal of Trauma and Acute Care Surgery Background: We have recently demonstrated the protective effects of electrical stimulation of the vagus nerve in prevention of gut injury after severe burn. Here we evaluate the potential for a pharmacologic agonist of the vagus nerve as an approach to regulate outcomes in preclinical models. We tested a new generation of guanylhydrazone-derived compounds, CPSI-121; a compound that may activate the parasympathetic nervous system through poorly understood mechanisms to determine whether we could prevent intestinal mucosal barrier breakdown. Methods: Male balb/c mice were subjected to a full-thickness, 30% total body surface area steam burn, and the efficacy of CPSI-121 was tested against vagus nerve stimulation (VNS) postburn at 4 hours. Surgical vagotomy was used to disrupt the neuroenteric axis and gut injury prevention was assessed. Gut barrier dysfunction was quantified by permeability to 4-kDa fluorescein isothiocyanate-dextran. Gut injury was assessed by histologic evaluation. Tight junction protein expression (ZO-1 and occludin) was characterized by immunofluorescence and immunoblot. Results: VNS and CPSI-121 administration significantly reduced the permeability to 4-kDa fluorescein isothiocyanate-dextran and maintained normal histology compared with burn. However, abdominal vagotomy eliminated the protective effects of both VNS and CPSI-121. ZO-1 and occludin expression was similar to sham in VNS and CPSI-121-treated burn animals, but significantly altered in burn-vagotomized animals. Splenectomy did not alter the effect of CPSI-121. Conclusion: Similar to direct electrical VNS, CPSI-121 effectively protects the intestinal mucosal barrier from breakdown after severe burn. We suggest that this could represent a noninvasive therapy to prevent end-organ dysfunction after trauma that would be administered during resuscitation. |
| Related Links | http://europepmc.org/articles/pmc4251782?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251782/pdf |
| Ending Page | 363 |
| Page Count | 9 |
| Starting Page | 355 |
| ISSN | 21630755 |
| e-ISSN | 21630763 |
| DOI | 10.1097/ta.0b013e31824484fe |
| Journal | The Journal of Trauma and Acute Care Surgery |
| Issue Number | 2 |
| Volume Number | 72 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2012-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: The Journal of Trauma and Acute Care Surgery Guanylhydrazone, Gut Injury, Burn, Tight Junction, Intestinal Barrier, Trauma |
| Content Type | Text |
| Resource Type | Article |
| Subject | Surgery Critical Care and Intensive Care Medicine |
