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Differentiation of oligodendrocyte precursor cells in adult spinal cord injury

成人脊髓损伤中少突胶质前体细胞的分化

基本信息

批准号：
15591604
负责人：
WATANABE Masahiko
金额：
$ 2.3万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

Because successful remyelination does not occur following traumatic spinal cord injury, patients suffer from long tract dysfunction. However, demyelination is followed by remyelination in early multiple sclerosis. Oligodendrocyte precursor cells constitute a large cell population in the adult mammalian central nervous system. We demonstrated the proliferation, migration, and differentiation of oligodendrocyte precursor cells in chemically induced demyelination, a model for multiple sclerosis, and reported that Nkx2.2 expression may regulate oligodendrocyte precursor cell differentiation, making it a key factor in the differentiation. To investigate what factors disturb remyelination in spinal cord injury, we examined the oligodendrocyte precursor cell proliferation and differentiation, and the expression of Nkx2.2 using contusive injury in rats as a model for traumatic spinal cord injury. This study showed that oligodendrocyte precursor cells proliferated after contusive injury but did … More not subsequently differentiate. The number of Nkx2.2-positive oligodendrocyte precursor cells did not significantly change in the tissue surrounding the lesion. Within the demyelinating lesion, the peak of Nkx2.2-positive oligodendrocyte precursor cell was delayed, and its level was lower than in the chemical models. No clearly recognizable oligodendrocytes were found in the demyelinating lesion throughout the observation period. To assess whether environmental changes differ between these two models, mRNA expressions of various cytokines were evaluated and compared. IL-1β and IL-6 mRNA significantly increased in the contusion-induced injury model, 6 h after the injury. These results suggest that environmental factors such as cytokines may affect Nkx2.2 expression or oligodendrocyte precursor cell differentiation in the contusion-induced spinal cord injury model. Additionally, the changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining. This results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination. Less

由于创伤性脊髓损伤后不会发生成功的再髓鞘形成，患者会遭受长束功能障碍的困扰。然而，在早期多发性硬化症中，脱髓鞘之后是重新髓鞘形成。在成年哺乳动物的中枢神经系统中，少突胶质前体细胞构成了一个庞大的细胞群。我们在多发性硬化的化学诱导脱髓鞘过程中证实了少突胶质前体细胞的增殖、迁移和分化，并报道了Nkx2.2的表达可能调节少突胶质前体细胞的分化，使其成为分化的关键因素。为了探讨是什么因素干扰了脊髓损伤后的髓鞘再生，我们采用大鼠挫伤模型，观察了少突胶质前体细胞的增殖分化和Nkx2.2的表达。本研究表明，挫伤后少突胶质前体细胞增殖，但…增殖。更不是随之而来的区别。Nkx2.2阳性的少突胶质前体细胞在病变周围组织中的数量没有明显变化。在脱髓鞘损伤中，Nkx2.2阳性的少突胶质前体细胞的高峰延迟，其水平低于化学模型。在整个观察期间，脱髓鞘病变中未发现明显可辨认的少突胶质细胞。为了评估这两种模型之间的环境变化是否不同，我们评估和比较了不同细胞因子的mRNA表达。挫伤模型伤后6h，IL-1mRNA和IL-6mRNA均显著升高。这些结果提示，在脊髓挫伤模型中，细胞因子等环境因素可能影响Nkx2.2的表达或少突胶质前体细胞的分化。免疫组织化学染色观察脱髓鞘病变中残留髓鞘碎屑水平的变化及活化巨噬细胞的浸润情况。这一结果提示，脊髓挫伤后活化巨噬细胞的延迟浸润与髓鞘碎屑的滞留有关，从而抑制了再髓鞘形成。较少