Yang‑Wuyue Liu1 • Jingyu Zhang2 • Wanda Bi1,5 • Mi Zhou1 • Jiabo Li1 • Tiantian Xiong1 • Nan Yang3  • Li Zhao4 • Xing Chen3 • Yuanguo Zhou3 • Wenhui He1 • Teng Yang1 • Hao Wang2 • Lunshan Xu2 • Shuang‑Shuang Dai

1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Army Medical University, Chongqing 400038, China

2 Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing 400042, China

3 Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, China

4 Department of Pathophysiology, College of High Altitude Medicine, Army Medical University, Chongqing 400038, China

5 Brigade 1 of Medical Undergraduates, School of Basic Medicine, Army Medical University, Battalion 1, Chongqing 400038, China

 

Abstract

    The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b+ pericytes after TBI. These CD11b+ pericyte subsets are characterized by increased permeability and pro-infammatory profles compared to CD11b– pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinfammation and BBB dysfunction after TBI. These data indicate that neutrophil–NET–pericyte and histone–Dectin-1–CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.

 

 

Keywords

Pericyte; Neutrophil; TBI; NET; Dectin-1

 

[SpringerLink]