scholarly journals Testing bioresorbable stent feasibility in a rat aneurysm model

2019 ◽  
Vol 11 (10) ◽  
pp. 1050-1054 ◽  
Author(s):  
Basil Erwin Grüter ◽  
Dominik Täschler ◽  
Fabio Strange ◽  
Jeannine Rey ◽  
Michael von Gunten ◽  
...  

BackgroundAdvances in stent-assisted coiling have incrementally expanded endovascular treatment options for complex cerebral aneurysms. After successful coil consolidation and aneurysm occlusion, endovascular scaffolds are no longer needed. Thus, bioresorbable stents that disappear after aneurysm healing could avoid future risks of in-stent thrombosis and the need for lifelong antiplatelet therapy.ObjectiveTo assess the applicability and compatibility of a bioresorbable magnesium- alloy stent (brMAS) for assisted coiling.MethodsSaccular sidewall aneurysms were created in 84 male Wistar rats and treated with brMAS alone, brMAS + aspirin, or brMAS + coils + aspirin. Control groups included no treatment (natural course), solely aspirin treatment, or conventional cobalt–chromium stent + coils + aspirin treatment. After 1 and 4 weeks, aneurysm specimens were harvested and macroscopically, histologically, and molecularly examined for healing, parent artery perfusion status, and inflammatory reactions. Stent degradation was monitored for up to 6 months with micro-computed and optical coherence tomography.ResultsAneurysms treated with brMAS showed advanced healing, neointima formation, and subsequent stent degradation. Additional administration of aspirin sustained aneurysm healing while reducing stent-induced intraluminal and periadventitial inflammatory responses. No negative interaction was detected between platinum coils and brMAS. Progressive brMAS degradation was confirmed.ConclusionsbrMAS induced appropriate healing in this sidewall aneurysm model. The concept of using bioresorbable materials to promote complete aneurysm healing and subsequent stent degradation seems promising. These results should encourage further device refinements and clinical evaluation of this treatment strategy for cerebrovascular aneurysms.

2005 ◽  
Vol 103 (5) ◽  
pp. 891-902 ◽  
Author(s):  
Gádor Cantón ◽  
David I. Levy ◽  
Juan C. Lasheras ◽  
Peter K. Nelson

Object. The goal of this study was to quantify the reduction in velocity, vorticity, and shear stresses resulting from the sequential placement of stents across the neck of sidewall cerebral aneurysms. Methods. A digital particle image velocimetry (DPIV) system was used to measure the pulsatile velocity field within a flexible silicone sidewall intracranial aneurysm model and at the aneurysm neck–parent artery interface in this model. The DPIV system is capable of providing an instantaneous, quantitative two-dimensional measurement of the velocity vector field of “blood” flow inside the aneurysm pouch and the parent vessel, and its changes at varying stages of the cardiac cycle. The corresponding vorticity and shear stress fields are then computed from the velocity field data. Three Neuroform stents (Boston Scientific/Target), each with a strut thickness between 60 and 65 µm, were subsequently placed across the neck of the aneurysm model and measurements were obtained after each stent had been placed. The authors measured a consistent decrease in the values of the maximal averaged velocity, vorticity, and shear stress after placing one, two, and three stents. Measurements of the circulation inside the sac demonstrated a systematic reduction in the strength of the vortex due to the stent placement. The decrease in the magnitude of the aforementioned quantities after the first stent was placed was remarkable. Placement of two or three stents led to a less significant reduction than placement of the first stent. Conclusions. The use of multiple flexible intravascular stents effectively reduces the strength of the vortex forming in an aneurysm sac and results in a decrease in the magnitude of stresses acting on the aneurysm wall.


Author(s):  
Tatsuro Saruga ◽  
Tadaatsu Imaizumi ◽  
Shogo Kawaguchi ◽  
Kazuhiko Seya ◽  
Tomoh Matsumiya ◽  
...  

AbstractC-X-C motif chemokine 10 (CXCL10) is an inflammatory chemokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Melanoma differentiation-associated gene 5 (MDA5) is an RNA helicase that plays a role in innate immune and inflammatory reactions. The details of the regulatory mechanisms of CXCL10 production and the precise role of MDA5 in RA synovitis have not been fully elucidated. The aim of this study was to examine the role of MDA5 in regulating CXCL10 expression in cultured human rheumatoid fibroblast-like synoviocytes (RFLS). RFLS was stimulated with Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA mimetic. Expression of interferon beta (IFN-β), MDA5, and CXCL10 was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay. A neutralizing antibody of IFN-β and siRNA-mediated MDA5 knockdown were used to determine the role of these molecules in regulating CXCL10 expression downstream of TLR3 signaling in RFLS. Poly I:C induced IFN-β, MDA5, and CXCL10 expression in a concentration- and time-dependent manner. IFN-β neutralizing antibody suppressed the expression of MDA5 and CXCL10, and knockdown of MDA5 decreased a part of CXCL10 expression (p < 0.001). The TLR3/IFN-β/CXCL10 axis may play a crucial role in the inflammatory responses in RA synovium, and MDA5 may be partially involved in this axis.


2004 ◽  
Vol 101 (5) ◽  
pp. 822-825 ◽  
Author(s):  
Dunyue Lu ◽  
Asim Mahmood ◽  
Changsheng Qu ◽  
Anton Goussev ◽  
Mei Lu ◽  
...  

Object. Atorvastatin, a β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects such as improving thrombogenic profile, promoting angiogenesis, and reducing inflammatory responses and has shown promise in enhancing neurological functional improvement and promoting neuroplasticity in animal models of traumatic brain injury (TBI), stroke, and intracranial hemorrhage. The authors tested the effect of atorvastatin on intracranial hematoma after TBI. Methods. Male Wistar rats were subjected to controlled cortical impact, and atorvastatin (1 mg/kg) was orally administered 1 day after TBI and daily for 7 days thereafter. Rats were killed at 1, 8, and 15 days post-TBI. The temporal profile of intraparenchymal hematoma was measured on brain tissue sections by using a MicroComputer Imaging Device and light microscopy. Conclusions. Data in this study showed that intraparenchymal and intraventricular hemorrhages are present 1 day after TBI and are absorbed at 15 days after TBI. Furthermore, atorvastatin reduces the volume of intracranial hematoma 8 days after TBI.


2009 ◽  
Vol 3 (4) ◽  
Author(s):  
Fangmin Xu ◽  
Kevin Hart ◽  
Claire E. Flanagan ◽  
John C. Nacker ◽  
Roham Moftakhar ◽  
...  

The treatment of cerebral aneurysms is frequently accomplished via endovascular delivery of metal coils in order to occlude the aneurysm and prevent rupture. This procedure involves imprecise packing of large lengths of wire into the aneurysm and often results in high rates of aneurysm recanalization. Over time, this incomplete aneurysm occlusion can lead to aneurysm enlargement, which may have fatal consequences. This report describes the fabrication and preliminary testing of a novel aneurysm occlusion device composed of a single metal coil surrounded by a biocompatible polymer shell. These coil-in-shell devices were tested under flow conditions in synthetic in vitro models of saccular aneurysms and deployed in vivo in a short-term porcine aneurysm model to study occlusion efficacy. A single nickel titanium shape memory wire was used to deploy a biocompatible, elastic polymeric shell, leading to aneurysmal sac filling in both in vitro and in vivo aneurysm models. The deployment of this coil-in-shell device in synthetic aneurysm models in vitro resulted in varying degrees of aneurysm occlusion, with less than 2% of trials resulting in significant leakage of fluid into the aneurysm. Meanwhile, in vivo coil-in-shell device implantation in a porcine aneurysm model provided proof-of-concept for successful occlusion, as both aneurysms were completely occluded by the devices. Both in vitro and in vivo studies demonstrated that this coil-in-shell device may be attractive as an alternative to traditional coil embolization methods in some cases, allowing for a more precise and controlled aneurysm occlusion.


2001 ◽  
Vol 10 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Berit L. Strand ◽  
Liv Ryan ◽  
Peter In't Veld ◽  
Bård Kulseng ◽  
Anne Mari Rokstad ◽  
...  

Alginate – poly-l-lysine (PLL) microcapsules can be used for transplantation of insulin-producing cells for treatment of type I diabetes. In this work we wanted to study the inflammatory reactions against implanted microcapsules due to PLL. We have seen that by reducing the PLL layer, less overgrowth of the capsule is obtained. By incubating different cell types with PLL and afterwards measuring cell viability with MTT, we found massive cell death at concentrations of PLL higher than 10 μg/ml. Staining with annexin V and propidium iodide showed that PLL induced necrosis but not apoptosis. The proinflammatory cytokine, tumor necrosis factor (TNF), was detected in supernatants from monocytes stimulated with PLL. The TNF response was partly inhibited with antibodies against CD14, which is a well-known receptor for lipopolysaccharide (LPS). Bactericidal permeability increasing protein (BPI) and a lipid A analogue (B-975), which both inhibit LPS, did not inhibit PLL from stimulating monocytes to TNF production. This indicates that PLL and LPS bind to different sites on monocytes, but because they both are inhibited by a p38 MAP kinase inhibitor, they seem to have a common element in the signal transducing pathway. These results suggest that PLL may provoke inflammatory responses either directly or indirectly through its necrosis-inducing abilities. By combining soluble PLL and alginate both the toxic and TNF-inducing effects of PLL were reduced. The implications of these data are to use alginate microcapsules with low amounts of PLL for transplantation purposes.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Yusuke Shimoda ◽  
Naoki Nakayama ◽  
Masaaki Hokari ◽  
Takeo Abumiya ◽  
Hideo Shichinohe ◽  
...  

Background and Purpose: Although recent researches on cerebral aneurysms (CAs) have been performed with the hydrodynamic or the molecular biological technique, the mechanisms of rupture are not fully understood. The aim of this study is to assess the mechanism by a comparison between ruptured and un-ruptured CAs with histopathological and electron-microscopic analysis. Methods: We analyzed 33 CAs (24 ruptured, 9 un-ruptured) collected surgically after neck clipping. As for the ruptured CAs, we operated them within 24 hours from the onset. HE staining, Elastica Masson staining, PTAH staining, and CD68 immunohistochemical staining were performed with paraffin sections. Morphological analysis with Scanning Electron Microscopy (SEM) was performed with 6 CAs (3 ruptured, 3 un-ruptured). Results: The common histopathological finding in both ruptured and un-ruptured CAs was that the aneurysmal wall consisted mostly of thick collagen layer without normal internal elastic lamina and media. The characteristic histopathological finding in ruptured CAs was inside intramural thrombus formation with infiltration of CD68 positive cells at the rupture point. The common SEM finding in both ruptured and un-ruptured CAs was the denudation of endothelial cells and the exposure of a subendothelial amorphous or a fibrous surface. The characteristic SEM finding in ruptured CAs was the cluster formation of thick fibrin fibers with incorporation of macrophages and platelets. Conclusions: While the endothelial denudation, the disappearance of internal elastic lamina and media, and the predominance of collagen layer in the aneurysmal wall were common in both ruptured and un-ruptured CAs, inside intramural thrombus formation with inflammatory reactions was characteristic only in ruptured CAs. This result suggests that thrombo-inflammatory reactions in CAs may act as a trigger for ruptures.


1993 ◽  
Vol 15 (1) ◽  
pp. 56-58 ◽  
Author(s):  
Takakazu Kawamata ◽  
Nobunhiko Aoki ◽  
Tatsuo Sakai ◽  
Koji Arai

2019 ◽  
Vol 2 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Atteqa Jawad ◽  
Richa Kaushal ◽  
Muhammad Sohail ◽  
Amna Yaqoob

Histamine is a neurotransmitter responsible for central regulation of inflammatory reactions. Initial studies were done by Sir Henry Dale in 1993. Histamine acts on its four type of receptors. H1 and H2 are well-established with pharmacological status. H1 receptors are mainly linked with inflammatory responses and developed to mitigate the inflammatory symptoms. While H2 antagonists are established with their role in decreasing basal gastric secretions by decreasing the cyclic adenylyl mono phosphate (cAMP), thus used as therapy line for gastric ulcers. H3 being located centrally imparts its central effects in cognitive functions that are pain, sleep, and memory modulation of neurotransmitters release including, dopamine, acetylcholine, noradrenalin and serotonin. H4 is discovered recently during cloning of H3 and found on immune related cells as, mast cells, T cells and dendrites. Experimental studies are helping in development of more pharmacologically worth drugs that can increase the quality of life.


2021 ◽  
Author(s):  
Li Guoquan ◽  
Du Junwei ◽  
He Qi ◽  
Fu Xinghao ◽  
Ji Feihong ◽  
...  

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.


2021 ◽  
Vol 39 ◽  
Author(s):  
Marlos Melo Martins ◽  
Arnaldo Prata-Barbosa ◽  
Maria Clara de Magalhães-Barbosa ◽  
Antonio José Ledo Alves da Cunha

ABSTRACT Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults.


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