التفاصيل البيبلوغرافية
| العنوان: |
Precision targeting of the vagal anti-inflammatory pathway attenuates the systemic inflammatory response to burn injury |
| المؤلفون: |
Costantini, Todd W, Coimbra, Raul, Weaver, Jessica L, Eliceiri, Brian P |
| المصدر: |
Journal of Trauma and Acute Care Surgery, vol 92, iss 2 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2022 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Digestive Diseases, Neurosciences, Physical Injury - Accidents and Adverse Effects, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Oral and gastrointestinal, Animals, Burns, Dextrans, Disease Models, Animal, Fluorescein-5-isothiocyanate, Intestinal Mucosa, Lung Injury, Male, Mice, Inbred C57BL, Neuroimmunomodulation, Permeability, Systemic Inflammatory Response Syndrome, Vagus Nerve, alpha7 Nicotinic Acetylcholine Receptor, cholinergic anti-inflammatory, alpha 7 nicotinic acetylcholine, intestine, Nursing |
| جغرافية الموضوع: |
323 - 329 |
| الوصف: |
BackgroundThe systemic inflammatory response (SIRS) drives late morbidity and mortality after injury. The α7 nicotinic acetylcholine receptor (α7nAchR) expressed on immune cells regulates the vagal anti-inflammatory pathway that prevents an overwhelming SIRS response to injury. Nonspecific pharmacologic stimulation of the vagus nerve has been evaluated as a potential therapeutic to limit SIRS. Unfortunately, the results of clinical trials have been underwhelming. We hypothesized that directly targeting the α7nAchR would more precisely stimulate the vagal anti-inflammatory pathway on immune cells and decrease gut and lung injury after severe burn.MethodsC57BL/6 mice underwent 30% total body surface area steam burn. Mice were treated with an intraperitoneal injection of a selective agonist of the α7nAchR (AR-R17779) at 30 minutes postburn. Intestinal permeability to 4 kDa FITC-dextran was measured at multiple time points postinjury. Lung vascular permeability was measured 6 hours after burn injury. Serial behavioral assessments were performed to quantify activity levels.ResultsIntestinal permeability peaked at 6 hours postburn. AR-R17779 decreased burn-induced intestinal permeability in a dose-dependent fashion (p < 0.001). There was no difference in gut permeability to 4 kDa FITC-dextran between sham and burn-injured animals treated with 5 mg/kg of AR-R17779. While burn injury increased lung permeability 10-fold, AR-R17779 prevented burn-induced lung permeability with no difference compared with sham (p < 0.01). Postinjury activity levels were significantly improved in burned animals treated with AR-R17779.ConclusionDirectly stimulating the α7nAchR prevents burn-induced gut and lung injury. Directly targeting the α7nAChR that mediates the cholinergic anti-inflammatory response may be an improved strategy compared with nonspecific vagal agonists. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt9fs193dj; https://escholarship.org/uc/item/9fs193djTest |
| الإتاحة: |
https://escholarship.org/uc/item/9fs193djTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.461D7334 |
| قاعدة البيانات: |
BASE |
