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Neurosurgical Review Feb 2023Intracranial aneurysm (IA) animal models are paramount to study IA pathophysiology and to test new endovascular treatments. A number of in vivo imaging modalities are... (Review)
Review
Intracranial aneurysm (IA) animal models are paramount to study IA pathophysiology and to test new endovascular treatments. A number of in vivo imaging modalities are available to characterize IAs at different stages of development in these animal models. This review describes existing in vivo imaging techniques used so far to visualize IAs in animal models. We systematically searched for studies containing in vivo imaging of induced IAs in animal models in PubMed and SPIE Digital library databases between 1 January 1945 and 13 July 2022. A total of 170 studies were retrieved and reviewed in detail, and information on the IA animal model, the objective of the study, and the imaging modality used was collected. A variety of methods to surgically construct or endogenously induce IAs in animals were identified, and 88% of the reviewed studies used surgical methods. The large majority of IA imaging in animals was performed for 4 reasons: basic research for IA models, testing of new IA treatment modalities, research on IA in vivo imaging of IAs, and research on IA pathophysiology. Six different imaging techniques were identified: conventional catheter angiography, computed tomography angiography, magnetic resonance angiography, hemodynamic imaging, optical coherence tomography, and fluorescence imaging. This review presents and discusses the advantages and disadvantages of all in vivo IA imaging techniques used in animal models to help future IA studies finding the most appropriate IA imaging modality and animal model to answer their research question.
Topics: Humans; Intracranial Aneurysm; Tomography, Optical Coherence; Computed Tomography Angiography; Magnetic Resonance Angiography
PubMed: 36786880
DOI: 10.1007/s10143-023-01953-1 -
Investigative Ophthalmology & Visual... Aug 2022Animal models of choroidal neovascularization (CNV) are extensively used to characterize the pathophysiology of chorioretinal diseases with CNV formation and to evaluate...
PURPOSE
Animal models of choroidal neovascularization (CNV) are extensively used to characterize the pathophysiology of chorioretinal diseases with CNV formation and to evaluate novel treatment strategies. This systematic review aims to give a detailed overview of contemporary animal models of CNV.
METHODS
A systematic search was performed in PubMed and EMBASE from November 20, 2015, to November 20, 2020, for mammalian animal models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol.
RESULTS
A total of 380 full articles, representing 409 independent animal models, were included. Mice were by far the most utilized animal (76%) followed by rats and non-human primates. The median age of rodents was 8 weeks but with a wide range. Male animals were used in 44% of the studies, but 32% did not report the sex. CNV was laser induced in 89% of the studies, but only 44% of these reported sufficiently on standard laser parameters. Surprisingly, 28% of the studies did not report a sample size for quantitative CNV evaluation. Less than half of the studies performed quantitative in vivo evaluation, and 73% evaluated CNV quantitatively ex vivo. Both in vivo and ex vivo evaluations were conducted primarily at day 7 and/or day 14.
CONCLUSIONS
The laser-induced mouse model is the predominant model for experimental CNV. The widespread use of young, healthy male animals may complicate clinical translation, and inadequate reporting challenges reproducibility. Definition and implementation of standardized methodologic and reporting guidelines are attractive.
Topics: Animals; Choroidal Neovascularization; Disease Models, Animal; Fluorescein Angiography; Laser Coagulation; Male; Mammals; Mice; Mice, Inbred C57BL; Rats; Reproducibility of Results
PubMed: 35943733
DOI: 10.1167/iovs.63.9.11 -
Translational Psychiatry Apr 2021Maternal immune activation (MIA) during pregnancy is recognized as an etiological risk factor for various psychiatric disorders, such as schizophrenia, major depressive... (Meta-Analysis)
Meta-Analysis Review
Maternal immune activation (MIA) during pregnancy is recognized as an etiological risk factor for various psychiatric disorders, such as schizophrenia, major depressive disorder, and autism. Prenatal immune challenge may serve as a "disease primer" for alteration of the trajectory of fetal brain development that, in combination with other genetic and environmental factors, may ultimately result in the emergence of different psychiatric conditions. However, the association between MIA and an offspring's chance of developing anxiety disorders is less clear. To evaluate the effect of MIA on offspring anxiety, a systematic review and meta-analysis of the preclinical literature was conducted. We performed a systematic search of the PubMed, Web of Science, PsycINFO, and Cochrane Library electronic databases using the PRISMA and World Health Organization (WHO) methodologies for systematic reviews. Studies that investigated whether MIA during pregnancy could cause anxiety symptoms in rodent offspring were included. Overall, the meta-analysis showed that MIA induced anxiety behavior in offspring. The studies provide strong evidence that prenatal immune activation impacts specific molecular targets and synapse formation and function and induces an imbalance in neurotransmission that could be related to the generation of anxiety in offspring. Future research should further explore the role of MIA in anxiety endophenotypes. According to this meta-analysis, MIA plays an important role in the pathophysiological mechanisms of anxiety disorders and is a promising therapeutic target.
Topics: Animals; Anxiety; Anxiety Disorders; Behavior, Animal; Depressive Disorder, Major; Disease Models, Animal; Female; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 33903587
DOI: 10.1038/s41398-021-01361-3 -
Advances in Nutrition (Bethesda, Md.) Sep 2017Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the... (Meta-Analysis)
Meta-Analysis Review
Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and fractures at other bone sites.
Topics: Animals; Body Mass Index; Disease Models, Animal; Hip Fractures; Humans; Non-Randomized Controlled Trials as Topic; Obesity, Abdominal; Prevalence; Risk Factors; Waist Circumference; Waist-Hip Ratio
PubMed: 28916573
DOI: 10.3945/an.117.015545 -
Cells May 2022Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is... (Review)
Review
Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.
Topics: Animals; Cognition; Encephalomyelitis, Autoimmune, Experimental; Glatiramer Acetate; Humans; Immunomodulation; Neuroprotection; Randomized Controlled Trials as Topic
PubMed: 35563884
DOI: 10.3390/cells11091578 -
International Journal of Molecular... Jul 2023The observation of neurogenic fever resulting from subarachnoid hemorrhage (SAH) in animal models is a useful tool for the interpretation of its pathophysiology in... (Review)
Review
The observation of neurogenic fever resulting from subarachnoid hemorrhage (SAH) in animal models is a useful tool for the interpretation of its pathophysiology in humans, which is still a major challenge in the management of neurocritical patients. This systematic review aims to identify the prognostic factors and pathophysiological elements that determine the onset of neurogenic fever and its severity in animal models. In addition, our study aims to analyze which pharmacological treatments are most effective. All the articles available in Pubmed, Embase, and the Biological Science Collection until August 2021 concerning in vivo experimental studies on SAH animal models, including full texts and abstracts written in English and Italian, were considered. The risk of bias was assessed with SYRCLE's Risk of Bias tool. In total, 81 records were retrieved; after excluding duplicates, 76 records were potentially relevant. A total of 64 articles was excluded after title and abstract screening. The remaining 12 studies were evaluated as full texts, and 6 other studies were excluded (SAH-induced animal studies without a body temperature assessment). In one study, body temperature was measured after SAH induction, but the authors did not report temperature recording. Therefore, only five studies met the search criteria. The high methodological heterogeneity (different animal species, different temperature measurement methods, and different methods of the induction of bleeding) prevented meta-analysis. Synthesis methodology without meta-analysis (SWiM) was used for data analysis. The total number of animals used as controls was 87 (23 rabbits, 32 mice, and 32 rats), while there were 130 animals used as interventions (54 rabbits, 44 mice, and 32 rats). The presence of blood in the subarachnoid space, particularly red blood cells, is responsible for neurogenic fever; the role of hemoglobin is unclear. The mechanism is apparently not mediated by prostaglandins. The autonomic nervous system innervating brown adipose tissue is undoubtedly implicated in the onset of neurogenic fever. The activation of the central adenosine-1 receptor is effective in controlling the temperature of animals with neurogenic fever (by inhibiting thermogenesis of brown adipose tissue).
Topics: Humans; Rats; Mice; Rabbits; Animals; Subarachnoid Hemorrhage; Autonomic Nervous System; Disease Models, Animal
PubMed: 37511267
DOI: 10.3390/ijms241411514 -
Nutrients Oct 2023Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle... (Review)
Review
Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D's positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery. The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population. Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery. However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D. In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery.
Topics: Aged; Humans; Animals; Mice; Vitamin D; Muscle, Skeletal; Vitamins; Vitamin D Deficiency; Muscular Diseases; Models, Animal; Regeneration
PubMed: 37892452
DOI: 10.3390/nu15204377 -
Experimental and Clinical... Mar 2023This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess... (Meta-Analysis)
Meta-Analysis Review
This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess the therapeutic effectiveness of stem cell transplant, using different transplant methods, injection sites, and stem cell types, and the reliability of this approach in different animal species. PubMed, the Cochrane Library, and Embase were searched for studies published from January 2006 to February 2022 that evaluated the use of stem cell transplant to treat azoospermia. We included 18 studies and conducted the analyses using Review Manager 5.2 software. Expression of the meiosis-related genes Vasa, Scp3, and Dazl and the average hematoxylin and eosin- positive staining area were improved after stem cell transplant. Subgroup analyses by mode of transplant showed higher expression of Scp3 and Dazl in the xenotransplant group. Although subgroup analyses by injection site showed that the seminiferous tubule group showed the most significant effect on Scp3 expression, spermatogenesis and repair of damaged testis were induced in the tunica albuginea group. The testicular torsion group also induced high levels of Scp3. Another subgroup analysis by stem cell type showed that umbilical cord mesenchymal stem cells promoted the highest expression of meiosis-related genes and successfully induced spermatogenesis and the repair of damaged testis. Urine-derived stem cells, spermatogonial stem cells, and amniotic fluid-derived stem cells showed significantly therapeutic effects; however, more studies are needed for definitive conclusions. Subgroup analyses by type of azoospermia animal model indicated that the use of stem cell transplant in rat or mouse models had an obvious therapeutic effect, but no significant therapeutic effect was seen in azoospermia hamsters. The meta-analysis confirmed that stem cell transplant can effectively treat azoospermia in animal models. Xenotransplant is shown to enhance the therapeutic effects of stem cell transplant on azoospermia.
Topics: Humans; Mice; Male; Rats; Animals; Azoospermia; Reproducibility of Results; Testis; Spermatogenesis; Meiosis
PubMed: 36987796
DOI: 10.6002/ect.2022.0327 -
Nutrients Oct 2022Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrinopathies. Evidence suggest that flavonoids have beneficial effects on endocrine and... (Meta-Analysis)
Meta-Analysis Review
Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrinopathies. Evidence suggest that flavonoids have beneficial effects on endocrine and metabolic diseases, including PCOS. However, high-quality clinical trials are lacking. We aimed to conduct a systematic review and meta-analysis of experimental studies to determine the flavonoids' effects in animal models of PCOS. Three electronic databases including PubMed, Scopus, and Web of Science were systematically searched from their inception to March 2022. The Systematic Review Center for Laboratory Animal Experimentation's risk of bias tool was used to assess methodological quality. The standardized mean difference was calculated with 95% confidence intervals as the overall effects. R was used for all statistical analyses. This study was registered in PROSPERO (registration number: CRD42022328355). A total of eighteen studies, including 300 animals, met the inclusion criteria. Our analyses demonstrated that, compared to control groups, flavonoid groups showed a significantly lower count of atretic follicles and cystic follicles and the count of corpus luteum was higher. A significant reduction in the luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), and free testosterone were observed in intervention groups. Nevertheless, there was no significant difference in the effects of flavonoids on the level of FSH, estradiol, and progesterone. Subgroup analyses indicated that the type of flavonoid, dose, duration of administration, and PCOS induction drug were relevant factors that influenced the effects of intervention. Current evidence supports the positive properties of flavonoids on ovarian histomorphology and hormonal status in animal models of PCOS. These data call for more randomized controlled trials and further experimental studies investigating the mechanism in more depth.
Topics: Animals; Estradiol; Female; Flavonoids; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Models, Animal; Polycystic Ovary Syndrome; Progesterone; Testosterone
PubMed: 36235780
DOI: 10.3390/nu14194128 -
Journal of Neuroscience Methods Feb 2016Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their... (Review)
Review
Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
Topics: Animal Experimentation; Animal Welfare; Animals; Disease Models, Animal; Epilepsy; Guidelines as Topic; Mice; Rats; Rodentia; United Kingdom
PubMed: 26376175
DOI: 10.1016/j.jneumeth.2015.09.007