Neuroimaging findings in preclinical amyotrophic lateral sclerosis models-How well do they mimic the clinical phenotype? A systematic review

被引:7
作者
Cannon, Amelia Elaine [1 ]
Zurrer, Wolfgang Emanuel [1 ]
Zejlon, Charlotte [2 ]
Kulcsar, Zsolt [3 ]
Lewandowski, Sebastian [4 ]
Piehl, Fredrik [4 ,5 ]
Granberg, Tobias [2 ,4 ]
Ineichen, Benjamin Victor [1 ,3 ,4 ]
机构
[1] Univ Zurich, Ctr Reproducible Sci, Zurich, Switzerland
[2] Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden
[3] Univ Zurich, Univ Hosp Zurich, Clin Neurosci Ctr, Dept Neuroradiol, Zurich, Switzerland
[4] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden
[5] Acad Specialist Ctr, Ctr Neurol, Stockholm Hlth Serv, Stockholm, Sweden
基金
瑞士国家科学基金会;
关键词
motor neuron disease (MND); magnetic resonance imaging (MRI); systematic review; amyotrophic lateral sclerosis; neuroimaging; external validity; 3R; neuroscience; G93A-SOD1 MOUSE MODEL; BRAIN-STEM NUCLEI; MOTOR-NEURON DEGENERATION; SPINAL-CORD; FRONTOTEMPORAL DEMENTIA; RELAXATION-TIME; ANIMAL-MODELS; CEREBRAL MRI; RAT MODEL; ALS;
D O I
10.3389/fvets.2023.1135282
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Background and objectives: Animal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND animal models to probe their external validity with regards to magnetic resonance imaging (MRI) features.Methods: In a comprehensive literature search in PubMed and Embase, we retrieved 201 unique publications of which 34 were deemed eligible for qualitative synthesis including risk of bias assessment.Results: ALS animal models can indeed present with human ALS neuroimaging features: Similar to the human paradigm, (regional) brain and spinal cord atrophy as well as signal changes in motor systems are commonly observed in ALS animal models. Blood-brain barrier breakdown seems to be more specific to ALS models, at least in the imaging domain. It is noteworthy that the G93A-SOD1 model, mimicking a rare clinical genotype, was the most frequently used ALS proxy.Conclusions: Our systematic review provides high-grade evidence that preclinical ALS models indeed show imaging features highly reminiscent of human ALS assigning them a high external validity in this domain. This opposes the high attrition of drugs during bench-to-bedside translation and thus raises concerns that phenotypic reproducibility does not necessarily render an animal model appropriate for drug development. These findings emphasize a careful application of these model systems for ALS therapy development thereby benefiting refinement of animal experiments.
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页数:8
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