Research Paper Volume 13, Issue 9 pp 13108—13123

Neutrophil extracellular traps, released from neutrophil, promote microglia inflammation and contribute to poor outcome in subarachnoid hemorrhage

Zeng Hanhai1, *, , Qin Bin1, *, , Zhou Shengjun1,3, *, , Li Jingbo1,2, , Guo Yinghan1, , Cai Lingxin1, , Cao Shenglong1, , Zhou Hang1, , Chen Huaijun1, , Zhuang Jianfeng1, , Peng Yucong1, , Fu Xiongjie1, , Yu Xiaobo1, , Tan Xiaoxiao1, , Li Jianru1, , Gu Chi1, , Yan Feng1, , Chen Gao1, ,

  • 1 Department of Neurological Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  • 2 Neurosurgerical Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
  • 3 Department of Neurological Surgery, Ningbo First Hospital, Ningbo, China
* Equal contribution

Received: January 19, 2021       Accepted: April 5, 2021       Published: May 8, 2021
How to Cite

Copyright: © 2021 Hanhai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Evidence indicates that neutrophil has promoted inflammation in several central nervous system diseases. However, whether the peripheral blood levels of neutrophils are associated with the functional outcome after subarachnoid hemorrhage and its potential mechanism remain unclear. In this study, we showed that neutrophil levels in peripheral blood were higher in patients with subarachnoid hemorrhage (P < 0.001) than in healthy subjects. Neutrophil levels were positively associated with Hunt and Hess grade (P < 0.001) and modified Rankin Scale scores at 3 months after SAH (P = 0.008). In terms of the mechanism, neutrophil extracellular traps markedly increased the proinflammatory subtype transition of microglia. After treatment with DNAse I, the proinflammatory subtype transition of microglia involving CD16 positive and IL-1β positive microglia was limited (P < 0.05). This mechanism was also verified in vitro. These results indicate that the existence of neutrophil extracellular traps, released from neutrophils after subarachnoid hemorrhage, can shift microglia toward a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in subarachnoid hemorrhage.


ANOVA: analysis of variance; BBB: blood–brain barrier; HH: Hunt and Hess; IACUC: Institutional Animal Care and Use Committee; IL: interleukin; mRS: modified Rankin Scale; NETs: neutrophil extracellular traps; PBS: phosphate-buffered saline; ROS: reactive oxygen species; SAH: subarachnoid hemorrhage; TNF: tumor necrosis factor.