Riemann Lennart, Younsi Alexander, Scherer Moritz, Zheng Guoli, Skutella Thomas, Unterberg Andreas W, Zweckberger Klaus
Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neuroanatomy, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
Front Neurol. 2018 Jun 8;9:428. doi: 10.3389/fneur.2018.00428. eCollection 2018.
Inflammation after traumatic spinal cord injury (SCI) is non-resolving and thus still present in chronic injury stages. It plays a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and development of neuropathic pain. Neural precursor cells (NPCs) have been shown to reduce the acute and sub-acute inflammatory response after SCI. In the present study, we examined effects of NPC transplantation on the immune environment in chronic stages of SCI. SCI was induced in rats by clip-compression of the cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post-injury. The functional outcome was assessed weekly for 8 weeks using the Basso, Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test. Afterwards, the rats were sacrificed, and spinal cord sections were examined for M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using immunofluorescence staining. Rats treated with NPCs had compared to the control group significantly fewer pro-inflammatory M1 macrophages and reduced immunodensity for inducible nitric oxide synthase (iNOS), their marker enzyme. Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In this model, the sub-acute transplantation of NPCs did not support survival and proliferation of M2 macrophages. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the altered microenvironment following NPC transplantation. Corresponding to these findings, reactive astrogliosis was significantly reduced in NPC-transplanted animals. Furthermore, we could observe a trend toward smaller cavity sizes and functional improvement following NPC transplantation. Our data suggest that transplantation of NPCs following SCI might attenuate inflammation even in chronic injury stages. This might prevent further neurodegeneration and could also set a stage for improved neuroregeneration after SCI.
创伤性脊髓损伤（SCI）后的炎症无法消退，因此在慢性损伤阶段仍然存在。它在SCI的病理生理学中起关键作用，并与进一步的神经退行性变和神经性疼痛的发展有关。神经前体细胞（NPCs）已被证明可减轻SCI后的急性和亚急性炎症反应。在本研究中，我们研究了NPC移植对SCI慢性期免疫环境的影响。通过对大鼠颈髓C6-C7水平进行夹压诱导SCI。在损伤后10天移植NPCs。使用Basso、Beattie和Bresnahan量表、CatWalk系统和网格行走测试，每周评估8周的功能结果。之后，处死大鼠，使用免疫荧光染色检查脊髓切片中的M1/M2巨噬细胞、T淋巴细胞、星形胶质细胞增生和细胞凋亡。与对照组相比，接受NPCs治疗的大鼠促炎性M1巨噬细胞明显减少，其标记酶诱导型一氧化氮合酶（iNOS）的免疫密度降低。SCI后8周，抗炎性M2巨噬细胞很少出现。在该模型中，NPCs的亚急性移植不支持M2巨噬细胞的存活和增殖。然而，NPC组的创伤后细胞凋亡明显减少，这可能是由于NPC移植后微环境改变所致。与这些发现一致，NPC移植动物的反应性星形胶质细胞增生明显减少。此外，我们可以观察到NPC移植后空洞尺寸有变小和功能改善的趋势。我们的数据表明，SCI后移植NPCs即使在慢性损伤阶段也可能减轻炎症。这可能预防进一步的神经退行性变，也可能为SCI后改善神经再生奠定基础。
