Differentiation of oligodendrocyte precursor cells in adult spinal cord injury

由于创伤性脊髓损伤后不会发生成功的髓鞘再生，因此患者遭受长束功能障碍。然而，在早期多发性硬化症中，脱髓鞘之后是髓鞘再生。少突胶质细胞前体细胞构成成年哺乳动物中枢神经系统中的大细胞群体。我们证明了少突胶质前体细胞在化学诱导的脱髓鞘（多发性硬化症的模型）中的增殖、迁移和分化，并报道Nkx2.2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。为了研究是什么因素干扰脊髓损伤后髓鞘再生，我们检测了少突胶质前体细胞的增殖和分化，以及Nkx2.2的表达，使用大鼠挫伤作为创伤性脊髓损伤的模型。这项研究表明，少突胶质细胞前体细胞在挫伤后增殖， 关于我们 而不是后来的分化。Nkx2.2阳性少突胶质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，Nkx2.2阳性少突胶质前体细胞的峰值延迟，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。为了评估这两种模型之间的环境变化是否不同，评估并比较了各种细胞因子的mRNA表达。在脑挫伤模型中，IL-1 β和IL-6 mRNA在伤后6h显著升高。这些结果表明，环境因素，如细胞因子可能会影响Nkx2.2的表达或少突胶质细胞前体细胞的分化在挫伤诱导的脊髓损伤模型。此外，通过免疫染色研究脱髓鞘病变中残留髓鞘碎片和活化巨噬细胞浸润水平的变化。这一结果表明，延迟浸润的活化巨噬细胞与持久性的髓鞘碎片后，挫伤性脊髓损伤，导致抑制髓鞘再生。少

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