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干细胞因子和粒细胞集落刺激因子促进严重创伤性脑损伤慢性期的髓鞘再生。

Stem Cell Factor and Granulocyte Colony-Stimulating Factor Promote Remyelination in the Chronic Phase of Severe Traumatic Brain Injury.

机构信息

Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

出版信息

Cells. 2023 Feb 23;12(5):705. doi: 10.3390/cells12050705.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c208/10000780/a77348dd7041/cells-12-00705-g001.jpg

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