Preclinical extracranial aneurysm models for the study and treatment of brain aneurysms: A systematic review.
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ABSTRACT:
SUBMITTER: Marbacher S
PROVIDER: S-EPMC7181093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their formation and progression are yet unclear and warrant preclinical studies. This systematic review aims to provide a comprehensive, systematic overview of available animal models for the study of IA pathobiology. We conducted a systematic literature search using the PubMed database to identify preclinical studies employing IA animal models. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were reviewed and categorized according to the experimental animal and aneurysm model. Of 4266 returned results, 3930 articles were excluded based on the title and/or abstract and further articles after screening the full text, leaving 123 studies for detailed analysis. A total of 20 different models were found in rats (nine), mice (five), rabbits (four), and dogs (two). Rat models constituted the most frequently employed intracranial experimental aneurysm model (79 studies), followed by mice (31 studies), rabbits (12 studies), and two studies in dogs. The most common techniques to induce cerebral aneurysms were surgical ligation of the common carotid artery with subsequent induction of hypertension by ligation of the renal arteries, followed by elastase-induced creation of IAs in combination with corticosterone- or angiotensin-induced hypertension. This review provides a comprehensive summary of the multitude of available IA models to study various aspects of aneurysm formation, growth, and rupture. It will serve as a useful reference for researchers by facilitating the selection of the most appropriate model and technique to answer their scientific question.
| S-EPMC7139747 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Previously, we showed that co-prevalence of extracranial carotid artery aneurysms (ECAAs) in patients with intracranial aneurysms (IAs) was 2% in a Dutch cohort. In order to obtain more precise estimates and discover potential predictors of ECAA co-prevalence in the European population, we retrospectively compared differences and similarities of our Dutch cohort with a Finnish cohort using protocolled imaging of the cerebrovascular tree. METHODS:IA patients within the prospective database of the Kuopio University Hospital were eligible for this study (n = 1,118). Image analysis and hospital chart review were conducted. RESULTS:In total, 458 patients with complete carotid imaging conform protocol were analyzed. Twenty-four ECAAs in 21 patients were identified (4.6%, 95% CI 2.9-6.9), a higher co-prevalence than in the Dutch cohort (1.9%; 95% CI 1.0-3.3), prevalence odds ratio (POR) 2.45 (95% CI 1.19-5.03). In the Finnish cohort, 25% of all ECAAs were located around the carotid bifurcation, others in the internal carotid artery distally from the bifurcation. Independent predictors for ECAA co-prevalence were origin of country (POR 2.41, 95% CI 1.15-5.06) and male gender (POR 2.25, 95% CI 1.09-4.64). CONCLUSION:The co-prevalence of ECAA in IA patients was twice as high in the Finnish compared to the Dutch IA cohort, with origin of country and male gender as independent predictors. Twenty-five percent of ECAAs would be missed, if the carotid bifurcation was not imaged. Therefore, we propose to always include imaging of the carotid bifurcation as the gold standard technique to identify ECAA in IA patients.
| S-EPMC6977743 | biostudies-literature
Project description:An extracranial carotid artery aneurysm (ECAA) is a rare condition. The major complications are rupture and thromboembolism. Therefore, treatment is generally recommended. We report the case of a young woman affected by an ECAA, with a cervical pulsatile mass. A multidisciplinary evaluation was performed to ensure the best treatment in terms of safety and efficacy, and the patient underwent hybrid treatment. The 6-month computed tomography angiogram revealed patency of the carotid artery stents and the venous graft, in the absence of any relevant complications. An ECAA is a serious clinical condition. The treatment is challenging, and a multidisciplinary evaluation and precise planning are recommended.
| S-EPMC10205765 | biostudies-literature
Project description:Background and purposePatient and aneurysm characteristics have been reported to differ between patients with familial and non-familial intracranial aneurysms (IAs), although results are inconsistent. We systematically reviewed and meta-analyzed the literature to identify and quantify patient- and aneurysm characteristics associated with familial IAs.MethodsWe searched PubMed and EMBASE for case-control and cohort studies comparing patient- and aneurysm characteristics between familial and non-familial IAs. Two observers independently assessed study eligibility and appraised quality with the Newcastle Ottawa Scale. With univariable weighted linear regression analysis we calculated β-coefficients with corresponding 95% confidence intervals (CIs) for ruptured and unruptured IAs combined and for ruptured IAs only. Heterogeneity was assessed with Higgins I2.ResultsA total of 15 articles were included in the meta-analysis in which 16,346 patients were analyzed with a total of 14,225 IAs. For ruptured and unruptured IAs combined, multiple IAs were more prevalent in familial (28.5%) than in non-familial IAs (20.4%; β = 0.10, 95% CI, 0.04 to 0.16; I2 0%). For ruptured IAs only, in familial patients IAs were more prevalent on the middle cerebral artery (41.1% versus 29.5%; β = 0.12, 95% CI, 0.01 to 0.24; I2 12%) and ruptured at a younger age (46.5 years versus 50.8 years; β = -5.00, 95% CI, -9.31 to -0.69; I2 98%) than in non-familial patients. No significant differences were found for the proportion of women, size of the aneurysm at time of rupture, smoking or hypertension.ConclusionThese results suggest that characteristics of familial and non-familial IAs show considerable overlap, yet differ on specific aspects. However, results for age at rupture showed considerable heterogeneity. These findings should be taken into consideration for future etiological research into IAs.
| S-EPMC6453525 | biostudies-literature
Project description:Animal models are necessary to develop and test innovations in aneurysm therapy before clinical introduction. This review aims at identifying the most likely candidates for standardizing preclinical testing of aneurysm devices. We systematically searched electronic databases for publications on animal aneurysm models from 1961-2008 to assess the methodologic quality of the studies and collect data on the patency and angiographic and pathologic outcomes of treatments. There has been a steady increase in the annual number of publications with time. Species that were most frequently used were dogs, rabbits, and rodents, followed by swine. Most publications are single-laboratory studies with variables and poorly validated outcome measures, a small number of subjects, and limited standardization of techniques. The most appropriate models to test for recurrences after endovascular occlusion were the surgical bifurcation model in dogs, and the elastase-induced aneurysm model in rabbits. A standardized multicenter study is needed to improve the preclinical evaluation of endovascular devices in aneurysm therapy.
| S-EPMC7963965 | biostudies-literature
Project description:Both aortic aneurysm and dissection are life threatening pathologies. In the lack of a conservative medical treatment, the only therapy consists of modifying cardiovascular risk factors and either surgical or endovascular treatment. Like many other cardiovascular diseases, in particular atherosclerosis, aortic aneurysm and dissection have a strong inflammatory phenotype. Inflammasomes are part of the innate immune system. Upon stimulation they form multi protein complexes resulting mainly in activation of interleukin-1β and other cytokines. Considering the gathering evidence, that inflammasomes are decisively involved in the emergence and progression of aortic diseases, inflammasome targeted therapy provides a promising new treatment approach. A systematic review following the PRISMA guidelines on the current preclinical data regarding the potential role of inflammasome targeted drug therapy as novel treatment option for aortic aneurysms and dissections was performed. Included were all rodent models of aortic disease (aortic aneurysm and dissection) evaluating a drug therapy with direct or indirect inhibition of inflammasomes and a suitable control group with the use of the same aortic model without the inflammasome targeted therapy. Primary and secondary outcomes were incidence of aortic disease, aortic rupture, aortic related death, and the maximum aortic diameter. The literature search of MEDLINE (via PubMed), the Web of Science, EMBASE and the Cochrane Central Registry of Registered Trials (CENTRAL) resulted in 8,137 hits. Of these, four studies met the inclusion criteria and were therefore eligible for data analysis. In all of them, targeting of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome effectively reduced the incidence of aortic disease and aortic rupture, and additionally reduced destruction of the aortic wall. Treatment strategies aiming at other inflammasomes could not be identified. In conclusion, inflammasome targeted therapies, more precisely targeting the NLRP3 inflammasome, have shown promising results in rodent models and deserve further investigation in preclinical research to potentially translate them into clinical research for the treatment of human patients with aortic disease. Regarding other inflammasomes, more preclinical research is needed to investigate their role in the pathophysiology of aortic disease. Protocol Registration: PROSPERO 2021 CRD42021279893, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279893.
| S-EPMC8811141 | biostudies-literature
Project description:Background and purposeChildren with brain aneurysms may be at higher risk than adults to develop new or enlarging aneurysms in a relatively short time. We sought to identify comorbidities and angiographic features in children that predict new aneurysm formation or enlargement of untreated aneurysms.Materials and methodsRetrospective analysis of the University of California-San Francisco Pediatric Aneurysm Cohort data base including medical records and imaging studies was performed.ResultsOf 83 patients harboring 114 intracranial aneurysms not associated with brain arteriovenous malformations or intracranial arteriovenous fistulas, 9 (8.4%) developed new or enlarging brain aneurysms an average of 4.2 years after initial presentation. Comorbidities that may be related to aneurysm formation were significantly higher in patients who developed new aneurysms (89%) as opposed to patients who did not develop new or enlarging aneurysms (41%; RR, 9.5; 95% CI, 1.9%-48%; P = .0099). Patients with multiple aneurysms at initial presentation were more likely than patients with a single aneurysm at presentation to develop a new or enlarging aneurysm (RR, 6.2; 95% CI, 2.1%-185; P = .0058). Patients who initially presented with at least 1 fusiform aneurysm were more likely to develop a new or enlarging aneurysm than patients who did not present with a fusiform aneurysm (RR, 22; 95% CI, 3.6%-68%; P = .00050). Index aneurysm treatment with parent artery occlusion also was associated with higher risk of new aneurysm formation (RR, 4.2; 95% CI, 1.3%-13%; P = .024). New aneurysms did not necessarily arise near index aneurysms. The only fatality in the series was due to subarachnoid hemorrhage from a new posterior circulation aneurysm arising 20 months after index anterior circulation aneurysm treatment in an immunosuppressed patient.ConclusionsPatients who presented with a fusiform aneurysm had a significantly greater incidence of developing a new aneurysm or enlargement of an index aneurysm than did those who presented with a saccular aneurysm. In our patient cohort, 8 of the 9 children who eventually developed new or enlarging brain aneurysms initially presented with fusiform aneurysm morphology. Other comorbidities or multiple aneurysms were also common in these patients at initial presentation.
| S-EPMC7964403 | biostudies-literature
Project description:BackgroundThe safety of extracranial-intracranial (EC-IC) bypass in the management of anterior circulation intracranial aneurysms (IAs) remains to be determined. This systematic review aims to summarize the existing evidence and provide guidance for the precise management of IAs.Data sourceWe constructed search strategies and comprehensively searched Pubmed, Medline, Embase, Web of science, and Cochrane library.MethodsThis systematic review was actualized according to the PRISMA statement. We evaluated study quality using the methodological index for non-randomized study (MINORS). Effect sizes were pooled using a random-effects model. Heterogeneity between studies was assessed using the I 2 test. Publication bias was assessed using the Egger's test. The registration number for this systematic review is CRD42023396730.ResultThis systematic review included a total of 21 articles, involving 915 patients. Postoperative bypass patency rate was 99% (95% CI 0.98-1.00); short-term follow-up was 98% (95% CI 0.94-1.00); long-term follow-up was 95% (95% CI 0.93-0.97). The long-term follow-up occlusion rate of saphenous vein was higher than that of radial artery (OR 6.10 95% CI 1.04-35.59). Short-term surgery-related mortality was 0.3% (95% CI 0.000-0.012); long-term follow-up was 0.4% (95% CI 0.000-0.013); The proportion of patients with a score of 0-2 on the modified Rankin Scale (mRS) during long-term follow-up was 92% (95% CI 0.86-0.98). The incidence rates of long-term follow-up complications were: ischemic 3% (95% CI 0.01-0.06); hemorrhagic 1% (95% CI 0.00-0.03); neurological deficit 1% (95% CI 0.00-0.03); other 3% (95% CI 0.01-0.06).LimitationMost of the included studies were retrospective studies. Studies reporting preoperative status were not sufficient to demonstrate postoperative improvement. Lack of sufficient subgroup information such as aneurysm rupture status.ConclusionEC-IC therapy for anterior circulation IAs has a high safety profile. Higher level of evidence is still needed to support clinical decision.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396730, identifier: CRD42023396730.
| S-EPMC10102499 | biostudies-literature
Project description:The extracranial carotid artery aneurysm (ECAA) is a rare pathology for which clinical treatment guidelines are lacking. In general, symptoms or growth of the aneurysm sac are thought to indicate intervention. ECAAs may present in a large variety of shapes and sizes, and conventional diameter measurements fail to indicate geometrical differences. Therefore, we propose a protocol to measure ECAA size by 3D volumetric assessment. The volumes of 40 ECAAs in computed tomography angiography (CTA) images were measured through manual segmentation, by two independent operators. Volumes of the entire internal carotid artery (ICA) and the ECAA were measured separately. Excellent inter- and intraoperator reliability was found for both ICA and ECAA volumes, with all intraclass correlation coefficients above 0.94. Bland-Altman analysis revealed normal differences for both inter- and intraoperator agreement. For all volumes, similarity of the segmentations was excellent. Outliers were explained by presence of intraluminal ECAA thrombus, which hampered identification of the aneurysm outer wall. These results implicate robustness of our protocol, which is designed as a step-up towards (semi)automatic volumetric measurements to monitor patients with ECAA. Future (semi)automatic volumetric assessments are recommended and such techniques can be developed and validated using the proposed protocol and manual reference segmentations.
| S-EPMC6542789 | biostudies-literature
Project description:BackgroundThe importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings.MethodsMEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE's risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol.DiscussionOur systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews.Systematic review registrationPROSPERO CRD42022367726.
| S-EPMC10029211 | biostudies-literature