小胶质细胞在Cuprizone所致髓鞘脱失动物模型中的双重性作用

小胶质细胞(microglia)是中枢神经系统(CNS)中固有的免疫监视细胞,是CNS的重要组成部分,构成CNS的第一道免疫防线。小胶质细胞活化是许多CNS疾病的重要病理特征之一,其在多发性硬化(MS)的发病过程中扮演重要角色。MS是以炎症反应、髓鞘脱失和轴突损伤为主要特征的CNS疾病,MS患者及实验动物脑内均可见活化的小胶质细胞,其作用机制复杂,具有致炎和抗炎双重作用。一方面小胶质细胞可通过促进吞噬、轴突再生、释放神经营养因子等作用促进髓鞘的再生修复;另一方面小胶质细胞还可通过释放炎性因子、自由基、蛋白酶等对神经元和胶质细胞发挥毒性作用。Cuprizone(双环己酮草酰二腙)所致髓鞘脱失动物模型是研究髓鞘再生修复的理想模型,了解小胶质细胞的双重性对于理解MS的发生发展,寻找疾病治疗靶点具有十分重要的理论和实际意义。在此本文对小胶质细胞在cuprizone所致髓鞘脱失动物模型中的双重性作用做一综述。

Dichotomous roles of microglia in cuprizone-induced demyelination in animal models of multiple sclerosis

Microglia are the inherent macrophages and immune surveillance cells in the central nervous system (CNS) and compose the first guard of immune defense in CNS. The activation of microglia is one of the pathological features of many CNS diseases and acts as an important role during the multiple sclerosis (MS) process. MS is a CNS disease characterized by neuroinflammatory infiltration, demyelination and axonal damage. Accumulation of activated microglia at the injury site has been observed in brains of MS patients and experimental animals with complicated mechanisms. Microglia have both detrimental and beneficial roles. For instance, microglia have been shown to recruit and reactivate T cells in the CNS and release many detrimental molecules such as proteases, inflammatory cytokines, and free radicals. Conversely, they have also been observed to aid in axonal regeneration and remyelination as well as assist in the clearance of inhibitory myelin debris. In addition, microglia have been shown to release a variety of neurotrophic factors. Cuprizone[oxalic acid bis(cyclohexylidene hydrazide)] is a well-known copper-chelating agent. Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions. Discussion on the detrimental and beneficial aspects of microglia in cuprizone animal models will serve to better understand the development of MS and find out new therapeutic targets. This review will further our understanding of the dichotomous roles of microglia in cuprizone-induced demyelination in animal models of multiple sclerosis.