共0篇 平均IF=NaN (-)更多分析

    加载中

    logo
    Precision Stroke Animal Models: the Permanent MCAO Model Should Be the Primary Model, Not Transient MCAO. McBride Devin W,Zhang John H Translational stroke research An argument for preclinical stroke research to make more use of the permanent middle cerebral artery occlusion (MCAO) model, rather than transient MCAO, is presented. Despite STAIR recommending permanent MCAO as the primary model, preclinical stroke research has not been listened. In 2012, Hossmann reported that 64% of the treatment studies for MCAO used prompt transient MCAO models and only 36% of the studies used permanent MCAO or gradual transient MCAO (i.e., embolic stroke model). Then, in 2014 and 2015, 88% of published basic science studies on large vessel occlusion used the transient MCAO model. However, this model only represents 2.5-11.3% of large vessel stroke patients. Therefore, the transient MCAO model, which mimics stroke with reperfusion, does not accurately reflect the majority of clinical stroke cases. Thus, once again, the argument for studying permanent MCAO as a primary model is made and supported. 10.1007/s12975-017-0554-2
    Validation of a preclinical animal model to assess brain recovery after acute stroke. Liu Peng,Tang Yong-Yong,Yang Xiao-Shuai,Dai Jie,Yang Min,Zhang Hong,Liu Yang,Yan Hong,Song Xiu-Yun European journal of pharmacology This study was to validate the animal model for the research in the stage of recovery and sequela of ischemic stroke. For its recognized many advantages and widespread applications, middle cerebral artery occlusion / reperfusion (MCAO/R) in Male Sprague-Dawley rats was chosen to be the foundation model. Then the weight of rats (260-330 g), the thread bolt type (2636/2838/3040/3043), the time of brain infarct (2/3 h) were tested to choose the larger infarct volume, higher Longa's score and model success rate through Longa's score and TTC staining. Finally, optimum condition of model was used in long period observing from 1 to 90 days after MCAO/R via five assessment of sensorimotor functions and TTC staining. The results showed that the optimal rat model of cerebral infarction in the stage of recovery and sequela of ischemic stroke maybe the model rats which were 300 g weight and MCAO with 3040 line-lock for 3 h before reperfusion. In these conditions, the Longa's score was 2.1 ± 0.2, and infarct volume was 23.0 ± 2.4%. The sensorimotor functional test of bilateral asymmetry had significant difference from 1 to 90 days, the test of grid-walking had significant difference from 1 to 60 days, while other tests had significant difference only at 1 day after MCAO/R. In conclusion, 3040-300 g-3 h was the most appropriate condition, and the appropriate index of sensorimotor functions were bilateral asymmetry and grid-walking test. 10.1016/j.ejphar.2018.07.035
    Animal Models of Focal Cerebral Ischaemia and Haemorrhagic Transformation: Considerations in Experimental Stroke Study Design. Shearer J A,Douglas A S,Kirby B P,Tatlisumak T,Doyle K M Current vascular pharmacology BACKGROUND:Ischaemic stroke is often complicated with haemorrhage within the infarct zone or in a remote location especially when treated with intravenous thrombolysis and/or thrombectomy. While these early recanalisation treatments are highly effective, some of the benefit is lost because of haemorrhagic complications and consequential neurological deterioration of the patients. A number of mechanisms have been described that mediate the haemorrhagic changes and several agents have been tested in experimental models for inhibiting post-stroke haemorrhage. METHODS:Here, we review and discuss the small animal models of focal cerebral ischaemia and postischaemic stroke haemorrhagic transformation and how these models can best be utilised for developing further insights as well as potential treatment approaches for this serious clinical complication. RESULTS:The need to use appropriate animal models with relevant stroke risk factors to improve the clinical relevance and applicability of findings is becoming ever more apparent. Current focal ischaemia models can be adapted for the study of haemorrhagic transformation post-stroke. CONCLUSION:A number of factors can be added to the animal model design to increase the incidence and/or severity of haemorrhagic transformation post-ischaemic stroke, which can improve clinical relevance, aid the study of the pathophysiology and the future development of novel interventions. 10.2174/1570161115666170906115300
    Animal models of ischemic stroke and their application in clinical research. Fluri Felix,Schuhmann Michael K,Kleinschnitz Christoph Drug design, development and therapy This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models. 10.2147/DDDT.S56071
    Animal models of ischaemic stroke and characterisation of the ischaemic penumbra. McCabe Christopher,Arroja Mariana M,Reid Emma,Macrae I Mhairi Neuropharmacology Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed. This article is part of the Special Issue entitled 'Cerebral Ischemia'. 10.1016/j.neuropharm.2017.09.022