Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Cells. 2023 Feb 23;12(5):705. doi: 10.3390/cells12050705.
Severe traumatic brain injury (TBI) causes long-term disability and death in young adults. White matter is vulnerable to TBI damage. Demyelination is a major pathological change of white matter injury after TBI. Demyelination, which is characterized by myelin sheath disruption and oligodendrocyte cell death, leads to long-term neurological function deficits. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) treatments have shown neuroprotective and neurorestorative effects in the subacute and chronic phases of experimental TBI. Our previous study has revealed that combined SCF and G-CSF treatment (SCF + G-CSF) enhances myelin repair in the chronic phase of TBI. However, the long-term effect and mechanism of SCF + G-CSF-enhanced myelin repair remain unclear. In this study, we uncovered persistent and progressive myelin loss in the chronic phase of severe TBI. SCF + G-CSF treatment in the chronic phase of severe TBI enhanced remyelination in the ipsilateral external capsule and striatum. The SCF + G-CSF-enhanced myelin repair is positively correlated with the proliferation of oligodendrocyte progenitor cells in the subventricular zone. These findings reveal the therapeutic potential of SCF + G-CSF in myelin repair in the chronic phase of severe TBI and shed light on the mechanism underlying SCF + G-CSF-enhanced remyelination in chronic TBI.
严重创伤性脑损伤（TBI）会导致年轻成年人长期残疾和死亡。白质容易受到 TBI 损伤。脱髓鞘是 TBI 后白质损伤的主要病理变化。脱髓鞘表现为髓鞘鞘破坏和少突胶质细胞死亡，导致长期神经功能缺陷。干细胞因子（SCF）和粒细胞集落刺激因子（G-CSF）治疗在实验性 TBI 的亚急性期和慢性期显示出神经保护和神经修复作用。我们之前的研究表明，联合使用 SCF 和 G-CSF 治疗（SCF + G-CSF）可增强 TBI 慢性期的髓鞘修复。然而，SCF + G-CSF 增强髓鞘修复的长期效果和机制仍不清楚。在这项研究中，我们发现严重 TBI 慢性期存在持续进行性的髓鞘丢失。在严重 TBI 的慢性期使用 SCF + G-CSF 治疗可增强同侧外囊和纹状体的髓鞘再生。SCF + G-CSF 增强的髓鞘修复与侧脑室下区少突胶质前体细胞的增殖呈正相关。这些发现揭示了 SCF + G-CSF 在严重 TBI 慢性期髓鞘修复中的治疗潜力，并阐明了 SCF + G-CSF 增强慢性 TBI 中髓鞘再生的机制。
