美国罗切斯特大学Maiken Nedergaard和Rashad Hussain共同合作，近期取得重要工作进展。他们研究发现，增强淋巴引流可减少创伤后脑水肿。相关研究成果2023年11月15日在线发表于《自然》杂志上。

据介绍，脑水肿与创伤性脑损伤（TBI）后的发病率和死亡率有关。TBI后去甲肾上腺素水平升高，去甲肾上腺素升高的幅度可以预测损伤的程度和死亡的可能性。类淋巴系统障碍既是脑损伤的特征，也是脑损伤的原因之一，但其与损伤相关的去甲肾上腺素激增的关系尚不清楚。

研究人员报告了急性创伤后水肿是由于去甲肾上腺素过度全身释放引起的淋巴液和淋巴液流动的抑制所致。这种TBI后的肾上腺素能风暴与颈部淋巴管收缩性降低有关，与淋巴液和淋巴液返回系统循环的减少一致。因此，在TBI小鼠模型中，泛肾上腺素能受体抑制使中心静脉压正常化，并部分恢复了淋巴结和颈部淋巴流，这些作用显著减少了脑水肿并改善了功能结果。

此外，创伤后肾上腺素能信号传导的抑制促进了创伤损伤细胞碎片的淋巴输出，显著减少了继发性炎症和磷酸化tau的积累。

总之，这些观察结果表明，靶向中枢淋巴流的去甲肾上腺素能控制可能为治疗急性TBI提供一种治疗方法。

附：英文原文

Title: Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema

Author: Hussain, Rashad, Tithof, Jeffrey, Wang, Wei, Cheetham-West, Arokoruba, Song, Wei, Peng, Weiguo, Sigurdsson, Bjrn, Kim, Daehyun, Sun, Qian, Peng, Sisi, Pl, Virginia, Kelley, Douglas H., Hirase, Hajime, Castorena-Gonzalez, Jorge A., Weikop, Pia, Goldman, Steven A., Davis, Michael J., Nedergaard, Maiken

Issue&Volume: 2023-11-15

Abstract: Cerebral oedema is associated with morbidity and mortality after traumatic brain injury (TBI)1. Noradrenaline levels are increased after TBI2,3,4, and the amplitude of the increase in noradrenaline predicts both the extent of injury5 and the likelihood of mortality6. Glymphatic impairment is both a feature of and a contributor to brain injury7,8, but its relationship with the injury-associated surge in noradrenaline is unclear. Here we report that acute post-traumatic oedema results from a suppression of glymphatic and lymphatic fluid flow that occurs in response to excessive systemic release of noradrenaline. This post-TBI adrenergic storm was associated with reduced contractility of cervical lymphatic vessels, consistent with diminished return of glymphatic and lymphatic fluid to the systemic circulation. Accordingly, pan-adrenergic receptor inhibition normalized central venous pressure and partly restored glymphatic and cervical lymphatic flow in a mouse model of TBI, and these actions led to substantially reduced brain oedema and improved functional outcomes. Furthermore, post-traumatic inhibition of adrenergic signalling boosted lymphatic export of cellular debris from the traumatic lesion, substantially reducing secondary inflammation and accumulation of phosphorylated tau. These observations suggest that targeting the noradrenergic control of central glymphatic flow may offer a therapeutic approach for treating acute TBI.

DOI: 10.1038/s41586-023-06737-7

Source: https://www.nature.com/articles/s41586-023-06737-7