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成功的再髓质不会发生，因此患者患有长时间功能障碍。然而，脱髓鞘之后是在早期多发性硬化症中再生的。少突胶质细胞前体细胞在成年哺乳动物中枢神经系统中构成大量细胞群。我们证明了化学诱导的脱髓鞘中少突胶质细胞前体细胞的增殖，迁移和分化，这是多发性硬化症的模型，并报道NKX2.2表达可能调节少突胶质细胞细胞分化，从而使其成为分化的关键因素。为了研究哪些因素在脊髓损伤中变分透明度，我们检查了少突胶质细胞前体细胞增殖和分化，以及使用连续损伤在大鼠中作为脊髓损伤的模型的NKX2.2的表达。这项研究表明，连续损伤后少突胶质细胞前体细胞增殖，但……随后没有区分。 NKX2.2阳性的寡胶质细胞前体细胞的数量在病变周围的组织中没有显着变化。在脱髓鞘病变中，延迟了NKX2.2阳性的少突胶质细胞前体细胞的峰值，其水平低于化学模型。在整个观察期间，在脱髓鞘病变中未发现明显可识别的少突胶质细胞。为了评估这两个模型之间的环境变化是否有所不同，评估并比较了各种细胞因子的mRNA表达。损伤后6小时，在挫伤诱导的损伤模型中IL-1β和IL-6 mRNA显着增加。这些结果表明，在挫伤引起的脊髓损伤模型中，诸如细胞因子等环境因素可能影响NKX2.2表达或少突胶质细胞前体细胞分化。此外，通过免疫染色研究了残留髓磷脂碎屑水平的变化以及脱髓鞘病变中活化巨噬细胞的浸润。该结果表明，激活的巨噬细胞的延迟浸润与续科SCI后的髓磷脂碎片的持久性有关，从而导致抑制remyelination。较少的