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: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: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:Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury. Controlled interventional studies of NSC therapy using animal models of perinatal brain injury were identified using MEDLINE and Embase. Primary outcomes were brain infarct size, motor, and cognitive function. Data for meta-analysis were synthesized and expressed as standardized mean difference (SMD) with 95% confidence intervals (CI), using a random effects model. We also reported secondary outcomes including NSC survival, migration, differentiation, and effect on neuroinflammation. Eighteen studies met inclusion criteria. NSC administration decreased infarct size (SMD 1.09; CI: 0.44, 1.74, P = .001; I2 = 74%) improved motor function measured via the impaired forelimb preference test (SMD 2.27; CI: 0.85, 3.69, P = .002; I2 = 86%) and the rotarod test (SMD 1.88; CI: 0.09, 3.67, P = .04; I2 = 95%). Additionally, NSCs improved cognitive function measured via the Morris water maze test (SMD of 2.41; CI: 1.16, 3.66, P = .0002; I2 = 81%). Preclinical evidence suggests that NSC therapy is promising for the treatment of perinatal brain injury. We have identified key knowledge gaps, including the lack of large animal studies and uncertainty regarding the necessity of immunosuppression for NSC transplantation in neonates. These knowledge gaps should be addressed before NSC treatment can effectively progress to clinical trial.
| S-EPMC8641092 | biostudies-literature
Project description:Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores. Analysis of EAE models, treatment schedules, single and total doses, routes of administration, and onset of treatment from pre-immunization up to 35 days after immunization revealed high heterogeneity. Total doses ranged from 0.1 to 360 mg/kg for observation times of up to 35 days after immunization. About half of experiments (142/253) used total doses of 10-70 mg/kg. Employing this range, we tested anti-Itga4 as a reference mAb at varying schedules and got no, mild or substantial EAE-score reductions, depending on the mouse strain and onset of the treatment. The result agrees with the range of outcomes achieved in 10 reported anti-Itga4 experiments. Studies comparing low and high doses of various mAbs or early vs. late onset of treatment did not reveal dose-effect or timing-effect associations, with a tendency towards better outcomes with preventive treatments starting within the first week after immunization. The systematic comparison allows for extraction of some "common" design characteristics, which may be helpful to further assess the efficacy of mAbs and role of specific targets in preclinical models of multiple sclerosis.
| S-EPMC5618641 | biostudies-literature
Project description:Alzheimer's disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid contained in a wide range of plant species, is repeatedly reported to exert neuroprotective effects in experimental animal AD models. However, a systematic analysis of methodological rigor and the comparison between different studies is still lacking. A systematic review uses a methodical approach to minimize the bias in each independent study, providing a less biased, comprehensive understanding of research findings and an objective judgement of the strength of evidence and the reliability of conclusions. In this review, we identified 14 studies describing the therapeutic efficacy of quercetin on animal AD models by electronic and manual retrieval. Some of the results of the studies included were meta-analyzed by forest plot, and the methodological quality of each preclinical trial was assessed with SYRCLE's risk of bias tool. Our results demonstrated the consistent neuroprotective effects of quercetin on different AD models, and the pharmacological mechanisms of quercetin on AD models are summarized. This information eliminated the bias of each individual study, providing guidance for future tests and supporting evidence for further implementation of quercetin into clinical trials. However, the limitations of some studies, such as the absence of sample size calculations and low method quality, should also be noted.
| S-EPMC7014205 | biostudies-literature