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，因此患者会出现长束功能障碍。然而，在早期多发性硬化症中，脱髓鞘随后是再髓鞘形成。少突胶质前体细胞在成年哺乳动物中枢神经系统中构成了一个庞大的细胞群。我们在多发性硬化症的化学诱导脱髓鞘模型中证明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。为了探讨影响脊髓损伤再髓鞘形成的因素，我们以大鼠创伤性脊髓损伤为模型，检测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，少突胶质前体细胞在挫伤后增殖，但随后没有分化。病变周围组织中nkx2.2阳性少突胶质前体细胞数量无明显变化。在脱髓鞘病变内，nkx2.2阳性少突胶质前体细胞峰值延迟，且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识别的少突胶质细胞。为了评估环境变化在这两种模型之间是否存在差异，我们评估和比较了各种细胞因子的mRNA表达。IL-1β和IL-6 mRNA在伤后6 h显著升高。提示细胞因子等环境因素可能影响挫伤脊髓损伤模型中Nkx2.2的表达或少突胶质前体细胞的分化。此外，免疫染色法观察脱髓鞘病变中残余髓鞘碎片水平的变化和活化巨噬细胞的浸润。该结果提示，活化巨噬细胞的延迟浸润与挫伤性脊髓损伤后髓鞘碎片的持续存在有关，从而抑制髓鞘再生。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