Modifications to the classical rat aortic ring model to allow vascular degeneration studies.
Ontology highlight
ABSTRACT:
SUBMITTER: Blot G
PROVIDER: S-EPMC7821348 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Microglial activation represents a hallmark of inflammatory retinal diseases like diabetic retinopathy. Anti-inflammatory and especially microglia modulating approaches have been proposed as therapies for these diseases. In this study, clodronate-coated liposomes were intravitreally injected to investigate the effects of increased microglial activation on vasoregression in a model of retinal degeneration. Clodronate-coated liposomes, injected twice over a period of 5 weeks to study the effects of long term clodronate treatment on microglial activation, vasoregression (acellular capillary formation and pericyte loss) and to identify the pathways mediating the observed effects.
2021-01-29 | GSE165743 | GEO
Project description:Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3- and 18-month-old male Sprague-Dawley rats. The adhesion molecules E- and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (GFAP), and cleaved caspase-3 were measured at 48 h after ischemia in the cerebral cortex and hippocampus using Western blot, qPCR and immunofluorescence techniques. Diametric expression of GFAP and a different morphological pattern of caspase-3 labelling, although no changes in the cell number, were observed in the neurons of young and old animals. Expression of E-selectin and CAMs was also modified in an age- and ischemia/reperfusion-dependent manner. The hippocampus and cerebral cortex had similar response patterns for most of the markers studied. Our data suggest that old and young animals present different time-courses of neuroinflammation and apoptosis after ischemic damage. On the other hand, these results suggest that neuroinflammation is dependent on age rather than on the different vulnerability described for the hippocampus and cerebral cortex. These differences should be taken into account in searching for therapeutic targets.
| S-EPMC4453934 | biostudies-literature
Project description:PurposeA strong association between retinal degeneration and obesity has been shown in humans. However, the molecular basis of increased risk for retinal degeneration in obesity is unknown. Thus, an animal model with obesity and retinal degeneration would greatly aid the understanding of obesity-associated retinal degeneration. The retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity are described.MethodsHistologic and immunohistochemical examination were performed on retinal sections of 2- to 12-month-old WNIN-Ob rats, and findings were compared with those of lean littermate controls. RNA from retinas of 12-month-old WNIN-Ob and lean littermate rats was used for microarray and qRT-PCR analysis.ResultsThe WNIN-Ob rats developed severe obesity, with an onset at approximately 35 days. Evaluation of retinal morphology in 2- to 12-month-old WNIN-Ob and age-matched lean littermate controls revealed progressive retinal degeneration, with an onset between 4 to 6 months of age. Immunohistochemical analysis with anti-rhodopsin, anti-cone opsin, and PSD-95 antibodies further confirmed retinal degeneration, particularly rod cell loss and thinner outer plexiform layer, in the obese rat retina. Gene expression by microarray analysis and qRT-PCR established activation of stress response, tissue remodeling, impaired phototransduction, and photoreceptor degeneration in WNIN-Ob rat retina.ConclusionsWNIN-Ob rats develop increased stress in retinal tissue and progressive retinal degeneration after the onset of severe obesity. The WNIN-Ob rat is the first rat model to develop retinal degeneration after the onset of obesity. This novel rat model may be a valuable tool for investigating retinal degeneration associated with obesity in humans.
| S-EPMC8728689 | biostudies-literature
Project description:BackgroundAortic dissection (AD) and aortic aneurysm (AA) are critical illnesses with an unclear pathogenetic mechanism that seriously threaten human life. Aortic medial degeneration (AMD) is the main pathological feature of AD and AA. Diseases of iron metabolism can cause a variety of physiological dysfunctions. In this study, we aimed to clarify the state of iron metabolism in patients with AD and AA, and to explore the effect of iron metabolism on AMD.MethodsA total of 200 patients with AD or AA, and 60 patients with hypertension were included in the study. Blood samples were drawn immediately when patients were admitted to the hospital. Aortic specimens from patients with Stanford type A AD were obtained at the time of surgery. The status of iron metabolism in the circulation and the aortic wall was analyzed. In addition, apolipoprotein E knockout mice were fed chow with a different iron content, and angiotensin II (Ang II) was used to induce AMD. Furthermore, transferrin receptor 1 knockout (TFR1-/-) mice were used to study the effects of iron deficiency (ID) on aortic development, to observe the effects of different iron metabolism status on the formation of AMD in mice, and to explore the cytoskeleton of vascular smooth muscle cells (VSMCs) under different iron metabolism.ResultsPatients with AMD were iron deficient. ID is associated with the development of AMD in hypertensive patients. Iron-deficient feeding combined with Ang II pumping promoted the formation of AMD and significantly shortened the survival time of mice. ID significantly impaired the cytoskeleton of VSMCs.ConclusionsOur results highlighted that ID was associated with the formation of AMD in patients with hypertension. In this study, we identified a novel mechanism behind VSMCs dysfunction that was induced by ID, thereby suggesting iron homeostasis as a future precaution in patients with hypertension based on its important role in the maintenance of VSMC function.
| S-EPMC7805404 | biostudies-literature
Project description:Double aortic arch (DAA) and pulmonary artery sling (PAS) are vascular ring formations that present in neonates and infants with symptoms of respiratory stenosis. The patient was a girl with suspected ventricular septal defect (VSD), right aortic arch (AA), left patent ductus arteriosus, and bilateral superior vena cava (SVC) on foetal echography in the first day of life. The girl was delivered at 40 weeks and 4 days of gestation. Ventricular septal defect, DAA, coarctation of the left AA, and bilateral SVC were diagnosed. Contrast-enhanced computed tomography at Day 16 revealed PAS with concurrent anomalous tracheal branching in addition to DAA. The right A2 segmental artery, which supplies the right upper pulmonary artery, showed abnormal branching from the left pulmonary artery (LPA). At 3 months of age, VSD patching, left AA resection distal to the root of the left subclavian artery, arterial ligament dissection, and LPA replacement were performed. Pulmonary artery sling coexists with anomalous branching of the trachea and abnormal branching of the right pulmonary artery (RPA). Our patient had an extremely rare case of DAA concurrent with PAS and presented with anomalous tracheal and RPA branching. We were concerned that increased pulmonary blood flow caused by the VSD would exacerbate tracheal displacement. Radical surgery at 3 months of age resulted in good postoperative progress.
| S-EPMC6601200 | biostudies-literature
Project description:BackgroundThe restorative effect of classical music was assessed on the cyclophosphamide-induced animal model of premature ovarian failure (POF).MethodsMozart's piano classical music (K.448) was used for up to 4 and 8 weeks. Rats were exposed to music 6 h every day using a stereo system with a volume of 65-70 dB. Sera and ovarian tissue samples were collected for the evaluation of FSH, LH, and E2 and histopathological examination. At the same time points, samples were taken from the hypothalamus and hippocampus to monitor the expression of Ntrk2, Crh, and Pomc using real-time PCR. Mating trial was performed to evaluate the fertility status of POF rats.ResultsHistopathological examination revealed a significant increase (p < 0.05) in the numbers of morphologically normal follicles at all the developmental stages in POF rats after music therapy compared to the POF group (p < 0.05). Music therapy decreased FSH and LH levels to near-to-normal levels conidied with elevation of E2 (p < 0.05). Ntrk2, Crh, and Pomc expressions were down-regulated in POF rats. Music therapy increasaed the expression of Ntrk2 in the hypothalamus of POF rats (p < 0.05). In contrast, Crh and Pomc failed to reach the detection limit before intervention and four weeks after the intervention however, these genes were expressed eight weeks after music therapy. Fertility status was increased (p < 0.05) in terms of litter size in POF rats after being exposed to music compared to the non-treated POF control group (p < 0.05).ConclusionResults showed that music can exert therapeutic effects on POF rats via the alteration of sex-related hormones.
| S-EPMC9647984 | biostudies-literature
Project description:Goldenhar syndrome (GS) or oculo-auriculo-vertebral dysplasia (OAVD), involves a wide variety of organ systems. Cardiovascular anomalies are among the frequent malformations. The purpose of this report is to introduce a male case of a dizygotic twin pregnancy with GS and right circumflex aortic arch (RCAA), severe coarctation, hypoplastic aortic arch, aberrant right subclavian artery, vascular ring, bilateral renal artery stenosis, and mild Dandy-Walker syndrome. The embryology of RCAA and coarctation is revisited.
| S-EPMC4189242 | biostudies-literature
Project description:BackgroundJoint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model.MethodsThe knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction.ResultsThe number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression.ConclusionsThe results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.
| S-EPMC7678279 | biostudies-literature
Project description:Elastin, the principal component of the elastic fiber of the extracellular matrix, imparts to vertebrate tissues remarkable resilience and longevity. This work focuses on elucidating dynamical and structural modifications of porcine aortic elastin exposed to glucose by solid-state NMR spectroscopic and relaxation methodologies. Results from macroscopic stress-strain tests are also presented and indicate that glucose-treated elastin is mechanically stiffer than the same tissue without glucose treatment. These measurements show a large hysteresis in the stress-strain behavior of glucose-treated elastin-a well-known signature of viscoelasticity. Two-dimensional relaxation NMR methods were used to investigate the correlation time, distribution, and population of water in these samples. Differences are observed between the relative populations of water, whereas the measured correlation times of tumbling motion of water across the samples were similar. (13)C magic-angle-spinning NMR methods were applied to investigate structural and dynamical modifications after glucose treatment. Although some overall structure is preserved, the process of glucose exposure results in more heterogeneous structures and slower mobility. The correlation times of tumbling motion of the (13)C-(1)H internuclear vectors in the glucose-treated sample are larger than in untreated samples, pointing to their more rigid structure. The (13)C cross-polarization spectra reveal a notably increased ?-helical character in the alanine motifs after glucose exposure. Results from molecular dynamics simulations are provided that add further insight into dynamical and structural changes of a short repeat, [VPGVG]5, an alanine pentamer, desmosine, and isodesmosine sites with and without glucose. The simulations point to changes in the entropic and energetic contributions in the retractive forces of VPGVG and AAAAA motifs. The most notable change is the increase of the energetic contribution in the retractive force due to peptide-glucose interactions of the VPGVG motif, which may play an important role in the observed stiffening in glucose-treated elastin.
| S-EPMC4390820 | biostudies-other
Project description:Purpose:Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. Methods:Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. Results:Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. Conclusions:This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.
| S-EPMC7329949 | biostudies-literature