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
- 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
Received: January 19, 2021 Accepted: April 5, 2021 Published: May 8, 2021
https://doi.org/10.18632/aging.202993How to Cite
Abstract
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.
Abbreviations
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.