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脑骨髓轴及其对慢性创伤性脑损伤的影响

Rodney M Ritzel^1,2, Yun Li¹, Yun Jiao³

¹Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Research square

|October 4, 2023

概括

创伤性脑损伤 (TBI) 导致持久的骨髓干细胞功能障碍,损害先天免疫力和神经功能. 这种慢性骨髓激活会影响恢复,并增加对进一步脑损伤的敏感性.

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:

创伤性脑损伤 (TBI) 破坏了系统免疫功能,导致神经炎症和神经退行.
TBI对骨髓 (BM) 造血干细胞/原生细胞 (HSPC) 的慢性影响及其对先天免疫和神经结果的影响仍然不清楚.

研究的目的:

调查TBI对BM HSPCs的长期影响.
确定TBI诱导的BM细胞变化如何影响先天免疫和神经功能.

主要方法:

来自TBI受伤或假老鼠的骨髓 (BM) 被移植到健康的辐射宿主中,以创建模拟老鼠.
在移植后8周和8个月,分析了基因组小鼠的髓状细胞功能,神经缺陷和神经炎症.
进行基因表达分析以确定TBI驱动的变化.

主要成果:

从TBI捐赠者 (TBI→WT) 接受BM的化学小鼠表现出骨髓状细胞,氧化应激增加,细胞减少.
在8个月后,TBI→WT小鼠表现出白血病,持续性免疫细胞功能障碍和神经系统缺陷.
基因表达揭示了BM驱动的神经炎症和神经病理学,增加了微质化和白细胞透,与二次TBI后更长的复合期相关.

结论:

创伤诱导BM干细胞/原生细胞池的慢性激活和渐进性功能障碍.
这种功能障碍导致先天免疫和神经功能长期缺陷.
与TBI相关的BM变化增加了对随后脑损伤的易感性.

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