The commensal microbiota has a high impact on health and disease by modulating the development and homeostasis of host immune system. Immune cells are involved in virtually every aspect of the wound repair process; however, the impact of commensal microbiota on skin wound healing is largely unknown. In this study, we evaluated the influence of commensal microbiota on tissue repair of excisional skin wounds by using germ-free (GF) Swiss mice. We observed that macroscopic wound closure rate is accelerated in the absence of commensal microbiota. Accordantly, histologically assessed wound epithelization was accelerated in GF in comparison with conventional (CV) Swiss mice. The wounds of GF mice presented a significant decrease in neutrophil accumulation and an increase in mast cell and macrophage infiltration into wounds. Interestingly, alternatively activated healing macrophage-related genes were highly expressed in the wound tissue of GF mice. Moreover, levels of the anti-inflammatory cytokine IL-10, the angiogenic growth factor VEGF and angiogenesis were higher in the wound tissue of those mice. Conversely, scarring and levels of the profibrogenic factor TGF-β1 were greatly reduced in GF mice wounded skin when compared with CV mice. Of note, conventionalization of GF mice with CV microbiota restored wound closure rate, neutrophil and macrophage accumulation, cytokine production, and scarring to the same extent as CV mice. Overall, our findings suggest that, in the absence of any contact with microbiota, skin wound healing is accelerated and scarless, partially because of reduced accumulation of neutrophils, increased accumulation of alternatively activated healing macrophages, and better angiogenesis at wound sites.
Endometriosis is a debilitating disease that still needs surgery to be confirmed. Endometriosis is associated with increased plasma levels of phosphatidylcholines. F-fluorocholine ([F]FCH) is a radiopharmaceutical that is metabolized to phosphatidylcholine inside the cells and can be traced by positron emission tomography (PET). Here we evaluate [F]FCH as a potential tool for the noninvasive diagnosis of peritoneal endometriosis. Adult female Wistar rats had autologous uterine fragments dissected and grafted to the peritoneal wall to model peritoneal endometriosis. Ex vivo biodistribution assay and PET imaging studies were performed 30 minutes after [F]FCH administration. The [F]FCH uptake was 3-fold higher in endometriotic implant tissues than in muscle or peritoneum. Positron emission tomography imaging revealed the grafted uterine tissue in contrast to surrounding structures. Region-of-interest analysis of the reconstructed images showed higher accumulation of [F]FCH by endometriotic lesions, 0.34 (0.04)% of injected dose per gram of tissue (ID/g), in comparison with muscle tissue, 0.08 (0.01)% ID/g. However, sham implants with fat tissue were also detectable in PET imaging. These preliminary findings of [F]FCH uptake by ectopic uterine tissue implants and their localization by PET imaging encourage the future evaluation of this technique to detect small superficial endometriosis lesions in humans. Study protocols need to be further perfected and adapted for tests in women with endometriosis.
The use of mouse and rat models in conjunction with anatomic functional imaging techniques has directly contributed to expanding knowledge about the complex pathophysiology of stroke. Therefore, this study aims to identify the most relevant mouse and rat models of stroke and how [18F]FDG/PET can contribute to this pathology study. A narrative review of the literature was performed to describe applications of positron emission tomography in conjunction with the radiopharmaceutical [18F]FDG in stroke models. PubMed, Scopus, and Web of Science were searched for relevant articles published between 2015 and 2022. In this study, we describe applications of positron emission tomography in combination with the radiopharmaceutical [18F]FDG in mouse and rat stroke models. The most commonly used model was middle cerebral artery occlusion (MCAO) in rats. This study demonstrates that using murine and rat models in conjunction with anatomic functional imaging techniques has directly contributed to expanding knowledge about the complex pathophysiology of stroke. In addition, they have been essential for studies aimed at discovering and developing therapeutic and prophylactic strategies for the disease.
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