't Hart Bert A, Amor Sandra
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Curr Opin Neurol. 2003 Jun;16(3):375-83. doi: 10.1097/01.wco.0000073940.19076.43.
A major hurdle in the research of neuroinflammatory disorders of the central nervous system is the inaccessibility of the organ. Thus investigation is limited to end-stage disease and systemic changes that occur during disease progression, neither of which may reflect the pathological process in the central nervous system. These factors may explain the lack of effective therapies in multiple sclerosis, a common chronic inflammatory disease of the central nervous system. To overcome such limitations approaches using more relevant animal models have been developed to study pathological mechanisms as well as the design of rational therapeutic strategies. This review describes the animal models used to study pathological processes leading to inflammation within the central nervous system that may be operating in multiple sclerosis and the use of these models in the design of more rational therapeutic strategies.
The clinical heterogeneity of multiple sclerosis as well as the finding of different pathological patterns suggests that multiple sclerosis may be a spectrum of diseases that may represent different pathological processes. This and the renewed interest in the extent of axonal damage has led to the development of more relevant animal models, such as those in nonhuman primates, that both reflect the spectrum of multiple sclerosis and allow the development of species-specific therapeutic approaches.
While many animal models are available, the use of relevant animal models that mimic either the different forms of multiple sclerosis or the spectrum of multiple sclerosis is critical to examine those factors, for example genes or proteins, that are of pathogenic relevance and can be used as targets for therapy.
中枢神经系统神经炎症性疾病研究中的一个主要障碍是该器官难以进行研究。因此,研究仅限于疾病终末期以及疾病进展过程中发生的全身变化,而这两者都可能无法反映中枢神经系统的病理过程。这些因素可能解释了多发性硬化症(一种常见的中枢神经系统慢性炎症性疾病)缺乏有效治疗方法的原因。为克服此类限制,已开发出使用更相关动物模型的方法来研究病理机制以及合理治疗策略的设计。本综述描述了用于研究可能在多发性硬化症中起作用的导致中枢神经系统内炎症的病理过程的动物模型,以及这些模型在设计更合理治疗策略中的应用。
多发性硬化症的临床异质性以及不同病理模式的发现表明,多发性硬化症可能是一系列代表不同病理过程的疾病。这一点以及对轴突损伤程度重新产生的兴趣导致了更相关动物模型的开发,例如非人类灵长类动物模型,这些模型既能反映多发性硬化症的范围,又能允许开发针对特定物种的治疗方法。
虽然有许多动物模型可用,但使用模拟多发性硬化症不同形式或范围的相关动物模型对于研究那些具有致病相关性且可作为治疗靶点的因素(例如基因或蛋白质)至关重要。