Characteristics of astrocytes in Fukuyama congenital muscular dystrophy.

由于基底膜异常导致的神经胶质限制区破坏被认为参与了福山先天性肌营养不良（FCMD）脑损伤的发生。胶质细胞边界由星形细胞端足形成，并被基膜覆盖。我们之前报道过口蹄疫脑中的未成熟星形胶质细胞可能无法参与基底膜的功能。我们对8例手足口病患者（包括2例胎儿）的大脑和延髓进行了氧化修饰终产物的免疫组化检查，以阐明手足口病脑内星形细胞的特征。非手足口病病例包括3例胎儿病例作为对照。在胎儿病例中，手足口病与对照组之间无显著差异。在儿童和成人病例中，晚期糖基化终产物在手足口病患者的大脑星形胶质细胞中呈弱阳性，尽管在大多数对照病例中呈阴性。其他氧化修饰内产物如4-羟基壬烯醛和8-羟基脱氧鸟苷，或非氧化途径形成的终产物如吡啶碱和甲基乙二醛没有差异。Mn超氧化物歧化酶阳性的星形细胞在口蹄疫病例中呈增加趋势。我们的数据表明，ffcmd的星形胶质细胞对氧化应激敏感，Mn SOD对氧化应激表现出反应性增加，似乎在脑损伤的形成中起重要作用。随着病例的积累，将进行定量分析，如Western blot杂交。

Disruption of the glia limitans due to abnormal basement membrane has been considered to be involved in the genesis of the brain lesion of Fukuyama congenital muscular dystrophy (FCMD). The glia limitans is formed by astrocytic endfeet and is covered with the basement membrane. We reported previously that immature astrocytes in the FCMD brain may not be able to participate in the function of the basement membrane. Immunohistochemical examination for oxidative modification endproducts was performed in the cerebrum and medulla oblongata of 8 FCMD cases including 2 fetal cases to elucidate the characteristics of astrocytes in the FCMD brain. Non-FCMD cases including 3 fetal cases were used for controls. In fetal cases, significant difference was not found between FCMD and control cases. In cases of children and adults, advanced glycation endproduct tended to be weakly positive in cerebral astrocytes of FCMD cases, although it was negative in most of the control cases. Difference was not found in other oxidative modification endoproducts such as 4-hydroxynonenal and 8-hydroxy deoxyguanosine, or endproducts formed by non-oxidative pathway such as pyrraline and methylglyoxal. Astrocytes positive for Mn superoxide dismutase tended to increase in FCMD cases. Our data suggest that astrocytes in FCMD, which seems to play a significant role for formation of the brain lesion, is sensitive to oxidative stress and Mn SOD shows reactive increase against oxidative stress. Quantitative analysis such as Western blot hybridization will be performed with more accumulation of cases.