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神经退行性疾病的小鼠模型:临床前影像学和神经血管组分。

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

机构信息

Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, Italy.

IBB, CNR, Via T. De Amicis 95, 80145, Napoli, Italy.

出版信息

Brain Imaging Behav. 2018 Aug;12(4):1160-1196. doi: 10.1007/s11682-017-9770-3.

DOI:10.1007/s11682-017-9770-3
PMID:29075922
Abstract

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurodegenerative disorders are very complicated and multifactorial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very difficult to be interpretated and often useless. Mouse models could be condiderated a 'pathway models', rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high field Magnetic resonance, Optical Imaging scanners and of highly specific contrast agents. Behavioral test are useful tool to characterize different animal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the different neurodegenerative disorders. Aim of this review is to focus on the different existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases.

摘要

神经退行性疾病因其普遍性、病理学、缺乏基于机制的治疗方法以及对个体的影响,给基础科学和临床医学带来了巨大的挑战。转化研究可能有助于神经退行性疾病的研究。老鼠已成为研究疾病机制的关键模型,这些机制部分可以模拟相应人类疾病的某些方面。神经退行性疾病非常复杂且多因素。在进行药物测试时必须考虑到这一点。大多数在老鼠身上进行的药物筛选都非常难以解释,而且通常是无效的。老鼠模型可以被视为“途径模型”,而不是整个人类疾病复杂结构的模型。由于高分辨率单光子发射计算机断层扫描(SPECT)、正电子发射断层扫描(PET)、高磁场磁共振、光学成像扫描仪和高度特异性对比剂的可用性,近年来,非侵入性体内成像在老鼠的临床前研究中引起了越来越多的兴趣。行为测试是用于描述神经退行性病理学不同动物模型的有用工具。此外,许多作者观察到与不同神经退行性疾病相关的血管病理特征。本文的目的是重点介绍神经退行性疾病的不同现有动物模型,描述用于诊断和描述这些疾病相关血管病理特征的行为测试和临床前成像技术。

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