在慢性实验性脑损伤后的双向神经免疫功能障碍
Rodney M Ritzel1,2, Yun Li3, Yun Jiao4
1Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Rodney.M.Ritzel@uth.tmc.edu.
Journal of neuroinflammation
|April 5, 2024
概括
创伤性脑损伤 (TBI) 慢性损害骨髓干细胞,导致长期免疫和神经系统缺陷. 这种功能障碍导致持续的神经炎症,并影响随后脑损伤的恢复.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 已知创伤性脑损伤 (TBI) 会导致急性和慢性免疫系统改变.
- 这些系统性免疫变化与TBI后的神经炎症和神经退行有关.
- 创伤损伤对骨髓 (BM) 造血干细胞/原生细胞的慢性影响及其对先天免疫和神经功能的影响在很大程度上仍未得到研究.
研究的目的:
- 为了研究TBI对BM血造干细胞/祖先细胞的长期影响.
- 确定TBI诱导的BM细胞的变化如何影响先天免疫和神经功能.
- 阐明BM细胞衍生物在TBI结果中的作用.
主要方法:
- 通过将TBI暴露或假老鼠的骨髓移植到被辐射宿主中来生成骨髓 (BM).
- 使用流细胞计,多重ELISA和NanoString技术评估免疫系统的变化.
- 通过受控的皮质冲击诱导TBI,并使用行为测试评估神经功能.
主要成果:
- 创伤诱导了BM LSK+细胞的慢性转录基因变化,影响了表观遗传和衰老途径.
- 化学小鼠 (TBI→WT) 呈现了髓状细胞氧化应激,减少了细胞形成,后来出现了白血病.
- 观察到持续的神经缺陷,神经炎症和神经病理学,与创伤后更长的复制期相关.
结论:
- 创伤导致BM干细胞/原生细胞池的慢性激活和渐进性功能障碍.
- 这种功能障碍导致了血液形成,先天免疫力和神经功能的长期缺陷.
- 创伤诱导的BM变化有助于对随后的脑损伤的敏感性发生变化.
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