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Animal models of stroke: translational potential at present and in 2050.

ABSTRACT: Translation from basic science bench research in ischemic stroke to bedside treatment of patients suffering ischemic stroke remains a difficult challenge. Despite literally hundreds of compounds and interventions that provide benefit in experimental models of cerebral ischemia, efficacy in humans remains to be demonstrated. The reasons for failure to translate the extensive positive basic science findings to successful clinical trials have been the focus of discussion for years. Some attribute the failure to flaws in clinical trial design, others question the predictive value of current animal models and some question the quality of preclinical data. It is likely that a combination of all these shortcomings have ultimately led to the failure. The purpose of this review is to analyze the commonly used animal models used in the field today, provide a framework for understanding the current state of basic science research in the ischemic stroke field and discuss a path forward.

SUBMITTER: Herson PS

PROVIDER: S-EPMC4266275 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Animal models of stroke: translational potential at present and in 2050.

Herson Paco S PS Traystman Richard J RJ

Future neurology 20140901 5

Translation from basic science bench research in ischemic stroke to bedside treatment of patients suffering ischemic stroke remains a difficult challenge. Despite literally hundreds of compounds and interventions that provide benefit in experimental models of cerebral ischemia, efficacy in humans remains to be demonstrated. The reasons for failure to translate the extensive positive basic science findings to successful clinical trials have been the focus of discussion for years. Some attribute t ...[more]

PMID: 25530721

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Project description:The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissues disorders mainly characterized by skin hyperextensibility, joint hypermobility and generalized tissue fragility. Currently, 14 EDS subtypes each with particular phenotypic features are recognized and are caused by genetic defects in 20 different genes. All of these genes are involved in the biosynthesis and/or fibrillogenesis of collagens at some level. Although great progress has been made in elucidating the molecular basis of different EDS subtypes, the pathogenic mechanisms underlying the observed phenotypes remain poorly understood, and consequentially, adequate treatment and management options for these conditions remain scarce. To date, several animal models, mainly mice and zebrafish, have been described with defects in 14 of the 20 hitherto known EDS-associated genes. These models have been instrumental in discerning the functions and roles of the corresponding proteins during development, maturation and repair and in portraying their roles during collagen biosynthesis and/or fibrillogenesis, for some even before their contribution to an EDS phenotype was elucidated. Additionally, extensive phenotypical characterization of these models has shown that they largely phenocopy their human counterparts, with recapitulation of several clinical hallmarks of the corresponding EDS subtype, including dermatological, cardiovascular, musculoskeletal and ocular features, as well as biomechanical and ultrastructural similarities in tissues. In this narrative review, we provide a comprehensive overview of animal models manifesting phenotypes that mimic EDS with a focus on engineered mouse and zebrafish models, and their relevance in past and future EDS research. Additionally, we briefly discuss domestic animals with naturally occurring EDS phenotypes. Collectively, these animal models have only started to reveal glimpses into the pathophysiological aspects associated with EDS and will undoubtably continue to play critical roles in EDS research due to their tremendous potential for pinpointing (common) signaling pathways, unveiling possible therapeutic targets and providing opportunities for preclinical therapeutic interventions.

Project description:BackgroundStroke is the leading cause of death in China, and predicting the stroke burden could provide essential information guiding the setting of medium- and long-term health policies and priorities. The study aimed to project trends associated with stroke burden in China through 2050, not only in terms of incidence and mortality but also for prevalence and disability-adjusted life years (DALYs).MethodsData on stroke rates in incidence, prevalence, deaths, and DALYs in China between 1990 and 2019 were obtained from a recent Global Burden of Disease study. Demographic-specific trends in rates over time were estimated using three models: the loglinear model, the Lee-Carter model, and a functional time series model. The mean absolute percentage error and the root mean squared error were used for model selection. Projections up to 2050 were estimated using the best fitting model. United Nations population data were used to project the absolute numbers through 2050.ResultsFrom 2019 to 2050, the crude rates for all measures of the stroke burden are projected to increase continuously among both men and women. We project that compared with those in 2019, the incidence, prevalence, deaths, and DALYs because of stroke in China in 2050 will increase by 55.58%, 119.16%, 72.15%, and 20.04%, respectively; the corresponding increases in number were 2.19, 34.27, 1.58, and 9.21 million. The age-standardized rate is projected to substantially decline for incidence (8.94%), death (40.37%), and DALYs (43.47%), but the age-standardized prevalence rate is predicted to increase by 10.82%. By 2050, the burden of stroke among the population aged ≥65 years will increase significantly: by 104.70% for incidence, by 218.48% for prevalence, by 100.00% for death, and by 58.93% for DALYs.ConclusionsWith the aging population in China increasing over the next three decades, the burden of stroke will be markedly increased. Continuous efforts are needed to improve stroke health care and secondary prevention, especially for older adults.

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Animal models of stroke: translational potential at present and in 2050.

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Animal models of stroke: translational potential at present and in 2050.

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